Systems and methods for enhancing or affecting neural stimulation efficiency and/or efficacy

ABSTRACT

Systems and methods for enhancing or affecting neural stimulation efficiency and/or efficacy are disclosed. In one embodiment, a system and/or method may apply electromagnetic stimulation to a patient&#39;s nervous system over a first time domain according to a first set of stimulation parameters, and over a second time domain according to a second set of stimulation parameters. The first and second time domains may be sequential, simultaneous, or nested. Stimulation parameters may vary in accordance with one or more types of duty cycle, amplitude, pulse repetition frequency, pulse width, spatiotemporal, and/or polarity variations. Stimulation may be applied at subthreshold, threshold, and/or suprathreshold levels in one or more periodic, aperiodic (e.g., chaotic), and/or pseudo-random manners. In some embodiments stimulation may comprise a burst pattern having an interburst frequency corresponding to an intrinsic brainwave frequency, and regular and/or varying intraburst stimulation parameters. Stimulation signals providing reduced power consumption with at least adequate symptomatic relief may be applied prior to moderate or significant power source depletion.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims the benefit of U.S. ProvisionalApplication No. 60/588,406, filed on Jul. 15, 2004 and incorporatedherein in its entirety by reference.

TECHNICAL FIELD

The present disclosure relates to adjusting time dependent deviceoperation parameters, location dependent device operation parameters,and/or waveform delivery parameters to affect neural stimulation energyconsumption and/or efficacy. More particularly, this disclosure relatesto systems and methods directed toward altering device operationcharacteristics.

BACKGROUND

Neural activity in the brain can be influenced by electrical energy thatis supplied from a waveform generator or other type of device. Variouspatient perceptions and/or neural functions can thus be promoted ordisrupted by applying an electrical or magnetic signal to the brain. Asa result, researchers have attempted to treat various neurologicalconditions using electrical or magnetic stimulation signals to controlor affect brain functions. For example, Deep Brain Stimulation (DBS) hasshown promising results for reducing some of the symptoms associatedwith Parkinson's Disease, which results in movement or muscle controlproblems and is debilitating to a great number of individuals worldwide.

Neural activity is governed by electrical impulses or “actionpotentials” generated in and propagated by neurons. While in a quiescentstate, a neuron is negatively polarized, and exhibits a resting membranepotential that is typically between −70 and −60 mV. Through electricalor chemical connections known as synapses, any given neuron receivesfrom other neurons excitatory and inhibitory input signals or stimuli. Aneuron integrates the excitatory and inhibitory input signals itreceives, and generates or fires a series of action potentials in theevent that the integration exceeds a threshold potential. A neuralfiring threshold may be, for example, approximately −55 mV. Actionpotentials propagate to the neuron's synapses, where they are conveyedto other neurons to which the neuron is synaptically connected.

A neural stimulation system may comprise a pulse generator and anelectrode assembly. One or more portions of a neural stimulation systemmay be implanted in a patient's body. For example, an implanted pulsegenerator may commonly be encased in a hermetically sealed housing andsurgically implanted in a subclavicular location. An electrode assemblymay be implanted to deliver stimulation signals to a stimulation site,and is electrically coupled to the pulse generator via biocompatiblysealed lead wires. A power source is contained within the housing of thepulse generator and is generally a battery.

Neural stimulation is generally delivered or applied to a patient inaccordance with a treatment protocol. Typically, a treatment protocolspecifies an optimal or best set of neural stimulation parametersdirected toward maximally alleviating one or more patient symptomsthrough neural stimulation applied in a continuous, generallycontinuous, or nearly continuous manner. Unfortunately, under aconventional treatment protocol, neural stimulation efficacy may wane ordegrade over time.

Since a battery has a finite charge storage capacity, a battery willexpire or become depleted, thereby interrupting the patient's treatment.Various types of neural stimulation systems may include a nonrechargablebattery that may last approximately two to three years. After animplanted battery is exhausted, another surgery is typically required toreplace the pulse generator. As with any surgery, complications mayarise, and subsequent incisions to the implanted site may provetroublesome due to scar tissue, implantation site sensitivities, and/orother conditions.

BRIEF DESCRIPTION OF THE DRAWINGS AND TABLES

FIGS. 1A-1C are schematic illustrations of neural stimulation systemsaccording to embodiments of the invention.

FIG. 2A is an internal block diagram of a stimulation signal generatoror an implantable pulse generator (IPG) according to an embodiment ofthe invention.

FIG. 2B is an internal block diagram of a stimulation signal generatoror an IPG according to another embodiment of the invention.

FIG. 3A is a graph illustrating several stimulation signal parametersthat may at least partially describe, define, or characterize astimulation signal or waveform according to an embodiment of theinvention.

FIG. 3B is a graph illustrating an occurrence distribution that maycorrespond to a stimulation signal parameter according to an embodimentof the invention.

FIG. 4 is a graph illustrating a set of pulse repetition frequencyvalues versus time generated based upon an iterative function inaccordance with an embodiment of the invention.

FIG. 5A is a scatter plot illustrating a mapping of equation valuescorresponding to a Lorenz type attractor to pulse particular repetitionfrequencies and pulse widths according to an embodiment of theinvention.

FIG. 5B is a graph illustrating a mapping of equation valuescorresponding to a Lorenz type attractor to pulse particular repetitionfrequencies and pulse widths according to another embodiment of theinvention.

FIG. 6 is a block diagram illustrating particular communication modesthat may be supported by a neural stimulation system according to anembodiment of the invention.

FIG. 7A is a graph illustrating an interruption, disabling, or cessationof stimulation signal generation, delivery, or application relative toan hours-based time domain according to an embodiment of the invention.

FIG. 7B is a graph illustrating an interruption, disabling, or cessationof stimulation signal generation in a seconds-based time domainaccording to an embodiment of the invention.

FIG. 7C is a graph illustrating an interruption, disabling, or cessationof stimulation signal generation in a subseconds-based time domainaccording to an embodiment of the invention.

FIG. 8A is a graph illustrating a theta-burst stimulation pattern inaccordance with an embodiment of the invention.

FIG. 8B is a graph illustrating a stimulation frequency modificationrelative to an hours-based time domain according to an embodiment of theinvention.

FIG. 8C is a graph illustrating a stimulation frequency modificationrelative to a seconds-based time domain according to an embodiment ofthe invention.

FIG. 8D is a graph illustrating a stimulation frequency function appliedin a seconds-based time domain according to an embodiment of theinvention.

FIG. 8E is a graph illustrating a stimulation frequency modificationrelative to a subseconds-based time domain according to an embodiment ofthe invention.

FIG. 9A is a graph illustrating a stimulation level, amplitude, ormagnitude modification relative to an hours-based time domain accordingto an embodiment of the invention.

FIG. 9B is a graph illustrating a stimulation level, amplitude, ormagnitude modification relative to a seconds-based time domain accordingto an embodiment of the invention.

FIG. 9C is a graph illustrating a stimulation level, amplitude, ormagnitude modification relative to a subseconds-based time domainaccording to an embodiment of the invention.

FIG. 10A is a graph illustrating a neural stimulation intensitymodulation according to an embodiment of the invention.

FIG. 10B is a graph illustrating a neural stimulation intensitymodulation according to another embodiment of the invention.

FIG. 11A is a schematic illustration corresponding to a set ofspatiotemporal electrical contact activation patterns according to anembodiment of the invention.

FIG. 11B is a schematic illustration corresponding to a set ofspatiotemporal stimulation signal polarity variations according toanother embodiment of the invention.

FIG. 12 is a flowchart illustrating various methods for reducing powerconsumption and/or affecting neural stimulation efficacy.

FIG. 13 is a flowchart illustrating various other and/or additionalmethods affecting power consumption and/or neural stimulation efficacy.

FIG. 14 is a flowchart illustrating various methods for adjusting,modifying, or updating a treatment program based upon evidence of acumulative, persistent, or semipersistent neurofunctional effect.

FIG. 15 is a flow chart illustrating methods for adjusting powerconsumption in accordance with further embodiments of the invention.

Table 1 provides a list of representative types of stimulation signalparameter variation modes that may be programmably selected inassociation with an IPG programming session.

DETAILED DESCRIPTION

Introduction

The following disclosure describes a system and method for affectingneural stimulation efficiency and/or efficacy. Various embodiments ofsystems and/or methods described herein may be directed towardcontrolling, adjusting, modifying, and/or varying one or more manners inwhich neural stimulation may be applied or delivered to a patient,thereby possibly 1) prolonging or extending the life and/or recharginginterval associated with a power source such as a battery; and/or 2)influencing, affecting, maintaining, or improving neural stimulationefficacy. The neural stimulation may comprise electrical and/or magneticstimulation signals, and may be defined in accordance with spatial,temporal, electrical, and/or magnetic signal parameters, properties,and/or characteristics.

The application of neural stimulation in accordance with particularembodiments of the invention may affect neural stimulation efficacy atone or more times through one or more mechanisms, which may beanalogous, generally analogous, or somewhat analogous to Long TermPotentiation (LTP) and/or Long Term Depression (LTD). The application ofneural stimulation in accordance with certain embodiments of theinvention may additionally or alternatively affect neural stimulationefficacy at one or more times by affecting neural processes that arerelated or generally related to tolerance, adaptation, habituation,and/or sensitization. One or more effects associated with or arisingfrom the application of neural stimulation in accordance with certainembodiments of the invention may correspond to neuroplastic,neuroregenerative, neuroprotective, and/or neurogenic effects.

In accordance with particular embodiments of the invention, the neuralstimulation may correspond to transcranial, cortical, subcortical,cerebellar, deep brain, spinal column, cranial or other peripheralnerve, and/or other types of stimulation. Such stimulation can beprovided, delivered, or achieved using a variety of devices and/ortechniques. By way of example, the neural stimulation can be applied ordelivered through the use of a neural stimulation device that can be,but does not necessarily have to be, implanted within the patient'sbody. Such a neural stimulation device may comprise a pulse generatorcoupled to at least one electrode assembly. In many cases, a main sourceof power for a neural stimulation device comprises a battery and/or acapacitor. Batteries that are employed for implantable neuralstimulators can store a finite amount of charge or energy. The exactlength of a battery's life depends upon battery usage, as well as thematerials used to construct the battery.

In accordance with various embodiments of the invention, a treatmentprogram may specify, define, and/or indicate one or more manners oftreating, affecting, or influencing one or more types of neurologicdysfunction, functional deficits, conditions, and/or symptoms in aneffective or adequate manner. A treatment program may comprise and/or bedefined in accordance with one or more neural stimulation procedures;drug, growth factor, neurotrophic agent, and/or other chemical substanceprocedures; behavioral therapy procedures; and/or patient assessmentprocedures, as further described below.

The length or duration of one or more portions of a treatment program,and possibly the type(s) and/or location(s) of applied neuralstimulation, may depend upon the nature, extent, and/or severity of thepatient's condition, functional deficits, and/or neurologic dysfunction;a degree of patient recovery or functional development over time; and/orembodiment details. A treatment program in accordance with variousembodiments of the present invention may facilitate and/or effectuate atleast some degree of symptomatic relief and/or restoration ordevelopment of functional abilities in patients experiencing neurologicdysfunction arising from neurological damage, neurologic disease,neurodegenerative conditions, neuropsychiatric disorders,neuropsychological (e.g., cognitive or learning) disorders, and/or otherconditions. Such neurologic dysfunction and/or conditions may correspondto Parkinson's Disease, essential tremor, Huntingon's disease, stroke,traumatic brain injury (TBI), Cerebral Palsy, Multiple Sclerosis, a painsyndrome (e.g., associated with a central and/or peripheral paincondition, such as phantom limb pain, trigeminal neuralgia, trigeminalneuropathic pain, sympathetically maintained pain, postsurgical pain, orother conditions), a memory disorder, dementia, Alzheimer's disease, anaffective disorder, depression, bipolar disorder, anxiety,obsessive/compulsive disorder, Post Traumatic Stress Disorder (PTSD), aneating disorder, schizophrenia, Tourette's Syndrome, Attention DeficitDisorder, a phobia, an addiction, autism, epilepsy, a sleep orsleep-related disorder, a hearing disorder, a language disorder, aspeech disorder (e.g., stuttering), epilepsy, migraine headaches,dysfunction associated with an autonomic system or internal organ,and/or one or more other disorders, states, or conditions.

In some embodiments, a treatment program may be directed toward longterm neural stimulation, for example, when directed toward treatingsignificantly or severely progressed conditions. In certain embodiments,a treatment program may involve one or more types of neural stimulationacross the duration of a patient's life. Alternatively, a treatmentprogram may be directed toward limited duration neural stimulation. Forexample, a treatment program may be applied over one or more limitedtime intervals that correspond to an extent of the patient's recovery orfunctional gain(s). Alternatively or additionally, a treatment programmay be applied over a predetermined number of days, weeks, months,and/or years; and/or a predetermined number of treatment sessions, forexample, twenty, thirty, fifty, or some other number of treatmentsessions in total. A treatment program may also temporally span anaccumulated or aggregate amount of time that stimulation has beenapplied (e.g., in a continuous, generally continuous, or interruptedmanner) or over some amount of time and/or some number of treatmentsessions. Various aspects of limited duration treatment programs aredescribed in U.S. application Ser. No. 10/606,202, entitled Methods andApparatus for Effectuating a Lasting Change in a Neural-Function of aPatient, filed on Jun. 24, 2003, incorporated herein in its entirety byreference.

In certain embodiments, a limited duration treatment program may beapplied to a patient; followed by an interruption period; followed byanother limited duration treatment program; possibly followed by anotherinterruption period, and so on. An interruption period may comprise oneor more rest, neural consolidation, strengthening, and/or activitypractice periods. The length or duration of any given interruptionperiod may depend upon patient condition; the nature of prescribed,allowable, or acceptable patient activities corresponding to theinterruption period; an extent to which one or more symptomatic benefitsis maintained or improved; and/or other factors.

In particular embodiments, a limited duration treatment program and/oran interruption period may involve peripheral or functional electricalstimulation (FES), during which electrical signals are applied toperipheral nerves and/or muscles. For example, in accordance with onetype of limited duration treatment program, a patient may undergo an FESsession (e.g., for approximately 5-45 minutes) prior to a cortical, deepbrain, spinal column, or vagal nerve stimulation session, which mayoccur in association or conjunction with a behavioral task or therapy. Alimited duration treatment program may additionally or alternativelyspecify that central nervous system (CNS) stimulation and FES may beapplied in a simultaneous, essentially simultaneous, or nearsimultaneous manner, for example, timed relative to each other inaccordance with a measured or estimated central—peripheral neural signalconduction time.

In accordance with one type of interruption period, a patient mayundergo periodic (e.g., daily) FES sessions before and/or after a givenlimited duration treatment program. The FES sessions may occur prior topatient performance or attempted performance of one or more muscularstrengthening tasks or other activities. In general, the characteristicsof any given limited duration treatment program and/or those of anyparticular interruption period may be based upon the nature and/orextent of a patient's neurologic dysfunction, an expected level ofpatient benefit, and/or embodiment details.

A method for treating a neurological condition of a patient inaccordance with a particular aspect of the invention includes applyingelectromagnetic stimulation to a patient's nervous system over a firsttime domain with a first wave form having a first set of parameters. Themethod can further include applying electromagnetic stimulation to thepatient's nervous system over a second time domain with a second waveform having a second set of parameters, wherein at least one parameterof the second set is different than a corresponding parameter of thefirst set. In one specific aspect, the second time domain can besequential to the first time domain. In another specific aspect,multiple second time domains can be nested within the first time domain.

The method can further include interrupting the application ofelectromagnetic stimulation between the first and second time domains,and selecting the at least one parameter of the second set to reducepower consumption due to electrical stimulation during the second timedomain, compared with power consumption due to electrical stimulationduring the first time domain. In still further aspects, theelectromagnetic stimulation during at least one of the time domains canbe varied aperiodically, for example, chaotically, or otherwise.

Apparatuses in accordance with further aspects of the invention caninclude a stimulation device having at least one stimulator (e.g., anelectrode) configured to be positioned in signal communication withneural tissue of a patient's nervous system. The apparatus can furtherinclude a signal generator and a signal communication link operativelycoupled between the stimulation device and the signal generator. Theapparatus can still further include a controller operatively coupled tothe signal generator. In one particular aspect, the controller can beconfigured to provide instructions to the signal generator that directan application of electromagnetic stimulation to the patient's nervoussystem over a first time domain with a first wave form having a firstset of parameters, and over a second time domain with a second wave formhaving a second set of parameters. At least one parameter of the secondset can be different than a corresponding parameter of the first set.

In other aspects, the controller can be configured to provideinstructions to the signal generator to direct an application ofelectromagnetic stimulation to the patient in a manner that variesaperiodically, for example, in a chaotic or other fashion. In stillanother aspect, the controller can be configured to provide instructionsto the signal generator to direct an application of electromagneticstimulation to the patient in a manner that varies at least generallysimilarly to naturally occurring brain wave variations. For example, thecontroller can be configured to provide instructions to direct anapplication of electromagnetic stimulation having a burst frequency andan intra-burst frequency greater than the burst frequency. In particularembodiments, characteristics of the intra-burst stimulation may varyfrom one burst to another. In other embodiments, the inter-burstfrequency can be generally similar to naturally occurring alpha, beta,gamma, delta, or theta brain wave frequencies.

Neural Stimulation Systems

FIG. 1A is a schematic illustration of a neural stimulation system 1000according to an embodiment of the invention. One or more portions of aneural stimulation system 1000 may be implanted in a patient 10 andconfigured to supply, apply, and/or deliver electrical signals or pulsesto one or more stimulation sites. In one embodiment, the neuralstimulation system 1000 comprises at least one stimulation signalgenerator, which may communicate with a programming unit 180. In variousembodiments, the stimulation signal generator may comprise anImplantable Pulse Generator (IPG) 100 and at least one electrodeassembly 150 that are coupled by a set of electrically conductive leadwires 155 or another suitable signal communication link. Depending uponembodiment details, lead wires 155 may be implanted and/or positionedsubcutaneously in a tunnel from a subclavicular region, along the backof the neck, and around a patient's skull 30. One or more electrodeassemblies 150 may be surgically located, placed, or positioned relativeto a set of stimulation sites, for example, at, within, and/or proximateone or more areas or regions to be stimulated. In other embodiments, thestimulation signal generator may comprise one or more microstimulators,such as a Bionic Neuron or BION™ (Advanced Bionics Corp., Sylmar,Calif.).

In general, a stimulation site may be defined as an anatomical locationor region at which neural stimulation signals may be applied to apatient. Application of stimulation signals to a stimulation site mayresult in the application or delivery of such signals to and/or throughone or more target neural populations, where such populations maycorrespond to a type of neurologic dysfunction. The number ofstimulation sites under consideration at any given time may depend uponthe nature of the patient's neurologic dysfunction and/or embodimentdetails. A stimulation site may correspond to a cortical, subcortical,deep brain, spinal column, cranial or other peripheral nerve, and/orother neural location, area, or region.

A set of target neural populations and/or stimulation sites may beidentified based upon one or more structural neuroanatomicallocalization procedures; and/or spatial and/or temporal functionalneuroanatomical localization procedures. Such procedures may involveMagnetic Resonance Imaging (MRI), functional MRI (fMRI), DiffusionTensor Imaging (DTI), Perfusion Weighted Imaging (PWI),Electroencephalography (EEG), and/or other techniques. A set of targetneural populations and/or stimulation sites may additionally oralternatively be identified based upon one or more anatomical landmarkidentification procedures, silent period analyses, coherence-basedanalyses, Transcranial Magnetic Stimulation (TMS) procedures, and/orother procedures. Sample manners of identifying a target neuralpopulation and/or a stimulation site are described in U.S. patentapplication Ser. No. 09/802,808, entitled “Methods and Apparatus forEffectuating a Lasting Change in a Neural-Function of a Patient,” filedon Mar. 8, 2001; U.S. patent application Ser. No. 10/410,526, entitled“Methods and Apparatus for Effectuating a Lasting Change in aNeural-Function of a Patient,” filed on Apr. 8, 2003; U.S. patentapplication Ser. No. 10/731,731, entitled “System and Method forTreating Parkinson's Disease and Other Movement Disorders,” filed onDec. 9, 2003; U.S. patent application Ser. No. 10/782,526, entitled“Systems and Methods for Enhancing or Optimizing Neural StimulationTherapy for Treating Symptoms of Parkinson's Disease and/or OtherNeurological Dysfunction,” filed on Feb. 19, 2004; and U.S. patentapplication Ser. No. 10/731,892, entitled “Methods for Treating and/orCollecting Information Regarding Neurological Disorders, IncludingLanguage Disorders,” filed on Dec. 9, 2003, each of which isincorporated herein by reference.

FIG. 1B is a schematic illustration of a neural stimulation system 1002according to another embodiment of the invention. Relative to FIG. 1A,like reference numbers may indicate like or analogous elements. In oneembodiment, the neural stimulation system 1002 comprises an IPG 100coupled to a first electrode assembly 150 and a second electrodeassembly 152. Each electrode assembly 150, 152 may correspond to adifferent stimulation site. For example, the first electrode assembly150 may be positioned to apply or deliver stimulation signals to one ormore portions of the primary motor cortex, while the second electrodeassembly 152 may be positioned to apply stimulation signals to one ormore portions of the premotor cortex, the supplementary motor area(SMA), Broca's area, and/or another neural area. As another example, thefirst electrode assembly 150 may be positioned to apply stimulationsignals to one or more portions of the prefrontal cortex, while thesecond electrode assembly 152 may be positioned to apply stimulationsignals to one or more portions of the motor cortex, the somatosensorycortex, the visual cortex, and/or another neural location.

FIG. 1C is a schematic illustration of a neural stimulation system 1004according to another embodiment of the invention. Relative to FIGS. 1Aand 1B, like reference numbers may indicate like or analogous elements.In one embodiment, the neural stimulation system 1004 comprises a firstand a second electrode assembly 150, 152, which may be positioned in thesame hemisphere or different hemispheres. In certain embodiments, theneural stimulation system 1004 may comprise additional electrodeassemblies, for example, a third electrode assembly 154 and a fourthelectrode assembly 156, which may be positioned in the same hemisphereor different hemispheres. Stimulation sites in different hemispheres maybe homologous or nonhomologous, depending upon the nature of thepatient's neurologic dysfunction and/or embodiment details. Dependingupon embodiment details, the neural stimulation system 1004 may compriseat least a first IPG 100, and possibly a second IPG 102. The first IPG100 may be coupled, for example, to the first and second electrodeassemblies 150, 152, while the second IPG 102 may be coupled to thethird and fourth electrode assemblies 154, 156. Accordingly, each IPGcan direct signals to different electrode assemblies. In otherembodiments different IPGs can direct signals over different timedomains, which are described later.

In certain embodiments, one or more electrode assemblies 150 mayadditionally or alternatively be positioned and/or configured to sense,detect, or monitor neuroelectric activity corresponding to a set ofmonitoring sites. A monitoring site may be identical to or differentfrom a stimulation site. In one embodiment, a single electrode assembly150 may be configured both for applying stimulation signals andmonitoring neuroelectric activity. In such an embodiment, stimulationand monitoring operations may typically occur in a sequential ortemporally interrupted manner. In certain embodiments, an electrodeassembly 150 may include one or more sensing elements to monitor, forexample, thermal, neurochemical, and/or other types of neural and/orneural correlate activity.

An electrode assembly 150 may carry one or more electrodes or electricalcontacts 160 configured to provide, deliver, and/or apply stimulationsignals to neural tissue, for example, one or more cortical regions ofthe patient's brain 20 and/or neural populations synaptically connectedand/or proximate thereto. Such electrical contacts 160 may additionallyor alternatively sense, detect, or monitor neuroelectric activity.Examples of electrode assemblies 150 suitable for cortical and/or othertypes of stimulation are described in U.S. patent application Ser. No.60/482,937, entitled “Apparatuses and Systems for Applying ElectricalStimulation to a Patient”, filed Jun. 26, 2003; and U.S. patentapplication Ser. No. 10/418,796, entitled “Methods and Systems EmployingIntracranial Electrodes for Neurostimulation and/orElectroencephalography,” filed on Apr. 18, 2003, both of which areincorporated herein by reference.

Depending upon embodiment details, an electrode assembly 150 maycomprise, include, and/or provide one or more stimulation signal returnelectrodes (i.e., electrodes that facilitate electrical continuity orprovide a current return path) that may be positioned relative to a oneor more of locations within and/or upon the patient's body. A returnelectrode may be positioned at a remote location relative to a set ofelectrodes or electrical contacts 160 configured to apply or deliverstimulation signals to a target neural population, thereby facilitatingthe delivery of unipolar stimulation signals to a target neuralpopulation one or more times. Representative unipolar stimulationprocedures and devices are described in U.S. application Ser. No.10/910,775, entitled Apparatus and Method for Applying Neurostimulationto a Patient, filed on Aug. 2, 2004, incorporated herein by reference inits entirety. In general, the configuration, characteristics, and/orplacement of an electrode assembly 150, a set of electrical contacts160, and/or a return electrode may depend upon the nature of thepatient's condition or underlying disorder(s), the type and/or severityof symptoms that the patient 10 experiences or exhibits, and/orembodiment details.

As shown in FIG. 1A, in some embodiments, a neural stimulation system1000 may further include one or more patient monitoring devices, units,and/or systems 200 configured to detect, record, monitor, indicate,characterize, measure, calculate, and/or assess signals, data, orinformation corresponding to a patient state, condition, function,and/or the severity of particular types of patient symptoms. Dependingupon embodiment details, one or more portions of a patient monitoringunit 200 may be external or internal to the patient 10. A patientmonitoring unit 200 may be configured for communication with an externalprogramming device 180. In one embodiment, portions of a patientmonitoring unit 200 may be incorporated into an IPG 100.

A patient monitoring unit 200 may comprise, for example, one or moredevices configured to measure, perform calculations upon, and/or analyzeparticular types of electrophysiological signals, such as EMG, EEG,and/or MEG signals. A patient monitoring unit 200 may alternatively oradditionally comprise a cerebral bloodflow monitor. In certainembodiments, a patient monitoring unit 200 may comprise a neural imagingsystem, for example, an MRI-based system, a PET system, and/or anoptical or other type of tomography system. In particular embodiments, apatient monitoring unit 200 may comprise one or more devices configuredto provide neural stimulation, for example, a TMS device. In someembodiments, a patient monitoring unit 200 may comprise a set of devicesconfigured to measure and/or calculate cerebro-muscular and/orcerebro-cerebral coherence and/or partial coherence; event-relateddesynchronization information; power and/or frequency spectrainformation; silent period (e.g., cortical and/or peripheral silentperiod) information; and/or other information.

A patient monitoring unit 200 may additionally or alternatively compriseone or more devices for facilitating characterization, assessment,and/or evaluation of particular symptoms and/or patient performancerelative to one or more behaviors, tasks, and/or tests. Such devices maycomprise, for example, motion sensors; accelerometers; force, torque,and/or strain sensors and/or gauges; and/or other devices. Thecollection of information indicative of the efficacy and/or efficiencyof neural stimulation may aid in selecting, defining, modifying,updating, and/or adjusting one or more portions of a treatment program.In certain embodiments, a patient monitoring unit 200 may be implementedin one or more manners described in U.S. patent application Ser. No.101782,526, entitled “Systems and Methods for Enhancing or OptimizingNeural Stimulation Therapy for Treating Symptoms of Parkinson's Diseaseand/or Other Neurological Dysfunction,” filed on Feb. 19, 2004,incorporated herein by reference.

In certain embodiments described herein, cortical stimulation isillustrated. However, various embodiments of the present invention mayemploy other or additional neural stimulation systems and/or devices,such as, but not limited to, systems and/or devices configured to applytranscranial electrical stimulation (TES); spinal column stimulation(SCS); vagal, cranial, and/or other peripheral nerve stimulation (VNS);cerebellar stimulation; and/or deep brain stimulation (DBS).

In such cases, an electrode assembly 150 may comprise one or moretranscranial, nerve cuff, penetrating, depth, deep brain, and/or othertypes of electrodes or electrode assemblies (not shown). For example, inan alternate embodiment, the electrode assembly 150 may be configured toposition electrodes, signal transfer devices, or electrical contacts 152relative to the vagus and/or other cranial nerve; a spinal columnregion; and/or a subcortical and/or a deep brain region. In certainembodiments, a treatment program may additionally or alternativelyinvolve TMS, in which case a neural stimulation system may comprise acoil-type arrangement for delivering magnetic stimulation signals to thepatient 10.

FIG. 2A is an internal block diagram of a stimulation signal generatoror an IPG 100 according to an embodiment of the invention. In oneembodiment, the IPG 100 comprises a hermetically sealed housing 106 thathouses a power source 102 as well as a controller 108, a telemetryand/or communication unit 110 a, and at least one signal or pulsegenerating unit 110 b. The IPG 100 may also comprise a switching unit110 c. Depending upon embodiment details, the IPG 100 may furthercomprise at least one programmable computer medium (PCM) 109, which maybe coupled to the controller 108, the telemetry/communication unit 110a, the pulse generating unit 110 b, and/or the switching unit 110 c. TheIPG 100 may additionally comprise at least one timing unit 112. Finally,in various embodiments the IPG 100 comprises at least one output orheader structure 104 that facilitates electrical and mechanical couplingto an electrode lead structure.

The power source 102 typically comprises a charge storage device such asa battery. In some embodiments, the power source 102 may additionally oralternatively comprise another type of device for storing charge orenergy, such as a capacitor. The controller 108, the PCM 109, thetelemetry/communication unit 110 a, the pulse generating unit 110 b, theswitching unit 110 c, and/or the timing unit 112 may comprise integratedcircuits and/or microelectronic devices that synergistically produce andmanage the generation, output, and/or delivery of stimulation signals.In certain embodiments, one or more elements within the IPG 100 (e.g.,the communication unit 110 a, the pulse generating unit 110 b, theswitching unit 110 c, and/or other elements) may be implemented using anApplication Specific Integrated Circuit (ASIC).

The timing unit 112 may comprise a clock or oscillator and/or circuitryassociated therewith configured to generate or provide a set of timingreference signals to the controller 108, the PCM 109, thetelemetry/communication unit 110 a, the pulse generating unit 110 b, theswitching unit 110 c, and/or one or more portions, subelements, orsubcircuits of the IPG 100. Such elements, subelements, and/orsubcircuits may correlate or synchronize one or more operations to oneor more timing reference signals, including the generation of othersignals in a manner understood by those skilled in the art.

The controller 108 may control, manage, and/or direct the operation ofelements within the IPG 100, possibly on a continuous, near-continuous,periodic, or intermittent basis depending upon embodiment details. Thecontroller 108 may comprise one or more portions of an integratedcircuit such as a processing unit or microprocessor, and may be coupledto a programmable computer medium (PCM) 109. The PCM 109 may compriseone or more types of memory including volatile and/or nonvolatilememory, and/or one or more data or signal storage elements or devices.The PCM 109 may store an operating system, program instructions, and/ordata. The PCM 109 may store treatment program information, IPGconfiguration information, and stimulation parameter information thatspecifies or indicates one or more manners of generating and/ordelivering stimulation signals in accordance with particular embodimentsof the invention.

The pulse generating unit 110 b may comprise hardware and/or softwarefor generating and outputting stimulation signals. FIG. 3A is a graphillustrating several stimulation signal parameters that may at leastpartially describe, define, or characterize a stimulation signal orwaveform according to an embodiment of the invention. A stimulus starttime to may define an initial point at which a stimulation signal isapplied to one or more target neural populations. In one embodiment, thestimulation signal may be a symmetric or an asymmetric biphasic waveformcomprising a set or series of biphasic pulses, and which may be defined,characterized, or defined by parameters including a pulse width t₁ for afirst pulse phase; a pulse width t₂ for a second pulse phase; and apulse width t₃ for a single biphasic pulse.

Stimulation signal parameters may also include a stimulus repetitionrate 1/t₄ corresponding to a pulse repetition frequency; a stimuluspulse duty cycle equal to t₃ divided by t₄; a stimulus burst time t₅that defines a number of pulses in a pulse train; and/or a pulse trainrepetition rate 1/t₆ that defines a stimulus burst frequency. Otherparameters may include peak current amplitude I₁ for the first pulsephase and a peak current amplitude I₂ for a second pulse phase. Thoseskilled in the art will understand that pulse amplitude may decay duringone or both pulse phases, and a pulse may be a charge-balanced waveform.Those skilled in the art will further understand that in an alternateembodiment, pulses can be monophasic or polyphasic. Moreover, in certainembodiments, a pulse train may comprise predetermined, pseudo-random,and/or aperiodic combinations of monophasic, biphasic, and/or polyphasicpulse sequences.

In some embodiments, a stimulation signal generator may generate oroutput a direct current (DC) signal. Such a signal may be appliedtranscranially at one or more times, either alone or in association withone or more other types of neural stimulation (e.g., VNS, corticalstimulation, or DBS). An example of a transcranial Direct CurrentStimulation (tDCS) neural stimulation system is described by W. Paulusin “Transcranial Direct Current Stimualtion,” chapter 26 of TranscranialMagnetic Stimulation and Transcranial Direct CurrentStimulation—supplements to Clinical Neurophysiology, vol. 56, Edited byW. Paulus et al., Elsevier Science.

In various embodiments, a stimulation signal generator or pulsegenerator 110 b may generate or output stimulation signals at one ormore suprathreshold and/or subthreshold amplitudes, levels, intensities,or magnitudes at one or more times. The application of neuralstimulation at a suprathreshold level may raise neural membranepotentials corresponding to a set of target neural populations such thatthe neural stimulation itself generates or elicits a sufficient orstatistically significant number of action potentials capable oftriggering a neural function corresponding to one or more such targetneural populations. In contrast, the application of neural stimulationat a subthreshold level may raise or generally raise membrane potentialscorresponding to a set of target neural populations while avoiding thegeneration of a sufficient or statistically significant number of actionpotentials capable of triggering a neural function corresponding to suchtarget neural populations as a result of the subthreshold stimulationalone. Thus, the subthreshold stimulation by itself, in the absence ofadditional neural input (e.g., arising from neurofunctionally relevantpatient behavior and/or additional stimulation signals), fails to drivea neural function corresponding to a target neural population orensemble to which it is directed.

Depending upon embodiment details, a subthreshold stimulation amplitudemay correspond to a particular fraction or percentage of a lowest ornear lowest test stimulation signal amplitude at which a patientexhibits a particular type of response such as a movement, a sensation,and/or generation of an electrophysiological signal. For example, if apatient exhibits a movement in response to a test stimulation signalapproximately equal to or just exceeding 6 mA, a treatment program mayindicate a subthreshold stimulation amplitude of 3 mA, or approximately50% of the patient's movement threshold. The magnitude of a subthresholdstimulation signal at any given time may depend upon the location and/orcharacteristics of a target neural population to which it is applied ordirected.

In some embodiments, the pulse generating unit 110 b may generate oroutput stimulation signals in accordance with one or more mathematicaloperations and/or functions upon or corresponding to particularstimulation signal parameters (e.g., a pulse width, a pulse repetitionfrequency, a peak amplitude, and/or a burst characteristic). Suchfunctions or operations may facilitate the generation of stimulationsignals exhibiting periodic, quasi-periodic, aperiodic, self-similar,chaotic, random, and/or pseudorandom characteristics at one or moretimes. In certain embodiments in which stimulation parameter values mayvary, one or more parameter values may be limited or bounded in theevent that the avoidance of unnecessary suprathreshold stimulation orsuprathreshold stimulation exceeding a given level or duration isdesirable. Appropriate limits or bounds may be determinedexperimentally, and/or estimated, e.g., through the use of one or moreestimation functions (which may be based upon empirical and/orstatistical information).

In certain embodiments, the pulse generating unit 110 b may generate oroutput stimulation signals having particular parameter values (e.g., apulse repetition frequency, a peak amplitude, and/or a burstcharacteristic) that are determined in accordance with a probabilityfunction or an occurrence distribution. An occurrence distribution mayapply within or across one or more time intervals or domains, forexample, a subseconds-based, seconds-based, minute-based, hours-based,or other type of time domain. In such embodiments, parameter values maybe magnitude and/or range limited.

FIG. 3B is a graph illustrating an exemplary occurrence distributionthat may correspond to a stimulation signal parameter according to anembodiment of the invention. An occurrence distribution may specify orindicate an occurrence frequency for one or more parameter values,possibly relative to corresponding parameter value ranges. Thus, for astimulation parameter such as an interpulse interval, the occurrencedistribution of FIG. 3B may specify a relative number of instances thatparticular interpulse intervals may occur within a given time intervalor domain (e.g., approximately 0.25 seconds, 1 second, 15 minutes, 1hour, or another time interval).

As indicated in FIG. 3B, within a time interval under consideration(e.g., 250 milliseconds), an interpulse interval of 8 milliseconds mayoccur 5 times; an interpulse interval of 10 milliseconds may occur 8times; an interpulse interval of 12 milliseconds may occur 6 times; aninterpulse interval of 14 milliseconds may occur 2 times; and interpulseintervals of 16 milliseconds and 18 milliseconds may each occur once.While the occurrence distribution shown in FIG. 3B is approximatelybinomial, the use of a particular type of occurrence distribution (e.g.,a Poisson, geometric, hypergeometric, or other type of distribution) maydepend upon embodiment details and/or the nature of a patient'sneurologic dysfunction.

As previously indicated, the pulse generating unit 110 b may generatestimulation signals exhibiting a set of random parameter characteristicsor values at one or more times. Herein, random parameter values maycorrespond to signals that are random, pseudo-random, quasi-random,random-like, or partially random with respect to one or more stimulationsignal parameters. In various embodiments, random parameter values maybe magnitude limited or bounded, and/or weighted relative to anoccurrence function or probability distribution. In one embodiment, thegeneration of random parameter values in accordance with an occurrencedistribution may result in a known or approximately known number ofinstances that particular parameter values occur within any given timeinterval under consideration, but a quasi-random ordering of parametervalues when one time interval is considered with respect to another timeinterval.

In certain embodiments, the pulse generating unit 110 b may generatestimulation signals exhibiting a set of quasi-periodic or aperiodicparameter characteristics or values at one or more times. Herein,aperiodic parameter values may correspond to signals that are aperiodic,nonperiodic, essentially aperiodic, approximately aperiodic,aperiodic-like, or partially aperiodic relative to one or morestimulation signal parameters.

In one embodiment, a pulse generating unit 110 b may be configured tooutput aperiodic stimulation signals based upon an iterative function,for example, a Mandelbrot or Julia set where an iterated value x at atime t may be determined by operating upon one or more parameter valuescorresponding to previous times. In one embodiment, an iterativefunction may have a form such as x_(t)=F(x_(t-k))+c. Such an equationmay exhibit periodic, self-similar, or chaotic behavior depending uponan initial or seed value of x₀ (that is, x_(t) at a time defined as “0”)and the value of the constant c. In an example embodiment, a series ofaperiodic parameter values may be generated in accordance with thefollowing Equation:x _(t) =x ² _(t-1)−1.90   [1]where x₀ may correspond, for example, to a value between 0 and 1.90. Inone embodiment, each successive value of x_(t) may correspond to astimulation parameter value in accordance with a mapping function and/ora relationship between established, limited, approximated, or estimatedmaximum and minimum values of x_(t) and a desired stimulation parametervalue range.

FIG. 4 is a graph illustrating a representative set of pulse repetitionfrequency values versus time generated based upon Equation 1 using x₀equal to 1.9, where x_(t) values falling between −1.90 and 1.71 aremapped to pulse repetition frequencies between 20 and 120 Hertz. Certainembodiments may additionally or alternatively employ one or more othertypes of mappings to the same and/or different stimulation parameters.Those skilled in the art will understand that parameter valuediscretization in accordance with any given mapping may depend upon thenature of a patient's neurologic dysfunction and/or embodiment details(e.g., pulse generator capabilities).

An iterative function capable of exhibiting aperiodic behavior mayfacilitate the repeatable delivery of aperiodic stimulation signalsequences to one or more target neural populations without storingentire sequences of individual stimulation signal parameter valuesacross time. An iterative function may facilitate the repeatabledelivery of aperiodic stimulation signal sequences or subsequences basedupon a minimal or near-minimal amount of stored informationcorresponding to a minimal or near-minimal number of previously appliedparameter values, eliminating undesired or unnecessary parameter valuestorage. Relative to the representative example above, a given aperiodicstimulation signal sequence or subsequence may be reapplied to a targetneural population based upon a seed or parameter value and a constantrather than an entire sequence of individually applied parameter valuesstored in memory. Similarly, continuation, resumption, or reapplicationof an aperiodic stimulation signal sequence or subsequence may be basedupon the retrieval of one or more stored stimulation signal parametervalues and possibly an associated set of constants that correspond to aprior point in time (e.g., an interruption or termination time).

Different aperiodic pulse sequences may be generated using differentvalues of x₀ and/or c. Depending upon embodiment details, successive x₀and/or c values may be selected (e.g., from possible values within aprestored list) or generated in a predetermined, pseudo-random, oraperiodic manner, possibly in accordance with allowable value rangesand/or a probability distribution.

An aperiodic function may additionally or alternatively exhibit anotherform. In one embodiment, a stimulation parameter value may be generatedbased upon a set of partial sums corresponding to a type of Weierstrassfunction that may be defined, for example, in accordance with thefollowing Equation: $\begin{matrix}{{x(t)} = {\sum\limits_{n = 0}^{q}{a^{n}*{\cos\left( {b^{n}*t} \right)}}}} & \lbrack 2\rbrack\end{matrix}$where 0<a<1, b>1, ab≧1, and q may equal, for example, 10.

Particular neural populations may communicate at one or more times in amanner that corresponds to metastable attractor dynamics: In oneembodiment, a set of stimulation parameter values may be generated basedupon one or more attractors, for example, a Lorenz, Duffing, or Rosslerattractor, which may be capable of exhibiting mathematically metastable,quasi-chaotic, or chaotic behavior. For example, the behavior of aLorenz-type attractor may be approximated using the following set ofEquations:x ₁(t+Δt)=x ₁(t)−a*x ₁(t)*Δt+a*x ₂(t)*Δt   [3a]x ₂(t+Δt)=x ₂(t)+b*x ₁(t)*Δt−x ₂(t)*Δt−x ₁(t)*x ₃(t)*Δt   [3b]x ₃(t+Δt)=x ₃(t)+x ₁(t)*x ₂(t)*Δt−c*x ₃(t)*Δt   [3c]where exemplary default values for a, b, and c may be 5.00, 15.00, and1.00, respectively, and exemplary default values for x₁(0), x₂(0), andx₃(0) may be 1.00, 0.50, and 2.00. 0ther exemplary default values for a,b, and c may be 10.00, 28.00, and 2.67, respectively. An exemplarydefault value for Δt may be 20 milliseconds. As used herein, the term“exemplary” is taken to mean “representative” or “sample” or “exampleof” or “illustrative,” as opposed to “ideal” or “archetypal.”

Values of x₁(t), x₂(t), and/or x₃(t) may be mapped to particularparameter values. FIG. 5A is an exemplary scatter plot corresponding toEquations 3a and 3b, where x₁(t) is mapped to pulse particularrepetition frequencies between approximately 20 and 120 Hertz, and x₂(t)is mapped to particular pulse widths between approximately 50 and 150microseconds using default values of a, b, and c of 5.00, 15.00, and1.00, respectively. Such a mapping may specify, for example, pulserepetition frequency/pulse width value pairs for stimulation signalssuccessively output by an IPG 100 across one or more time periods. Thetypes of mappings described above may apply to other or additionalstimulation signal parameters.

In one embodiment, mappings such as those described above may occur inaccordance with one or more temporal offsets. FIG. 5B is an exemplarygraph corresponding to Equations 3a and 3b, where x₁(t) is mapped topulse repetition frequencies between approximately 20 and 120 Hertz, andx₂(t) is mapped to pulse widths between approximately 50 and 150microseconds using default values of a, b, and c of 10.00, 28.00, and2.67, respectively. At any given stimulation signal application timealong the x axis of FIG. 5B, a temporal offset of 15* Δt exists relativeto an x₁(t) mapping to a pulse repetition frequency value and an x₂(t)mapping to a pulse width. In such an embodiment, the pulse generatingunit 110 b may save previously generated values of x₁(t), x₂(t), and/orx₃(t) to facilitate a temporally offset stimulation signal parametermapping.

Certain embodiments of the invention may generate or output multiplestimulation parameter values based upon particular aperiodic, random,and/or other functions and/or operations in a simultaneous, generallysimultaneous, sequential, or intermittent manner. For example, a peakamplitude may be mapped to values between 2.0-8.0 mA in accordance withan aperiodic function; a first phase pulse width may be mapped to valuesbetween 50-250 microseconds in an accordance with an aperiodic functionor a pseudorandom operation; and/or a pulse repetition frequency may begenerated based upon an aperiodic, random, sinusoidal, or other functionto have values between 1-20 Hertz.

To aid ease of understanding, square waveforms and/or sinusoidalwaveforms are employed for purpose of example in particular portions ofthe description below. However, various embodiments of the presentinvention may employ, generate, apply, or deliver stimulation signalsexhibiting essentially any type of signal or waveform characteristic atone or more times (e.g., a biphasic waveform, a triangular waveform,and/or other types of waveforms) without departing from the scope of theinvention.

Referring again to FIG. 2A, in certain embodiments, the switching unit110 c comprises a switch matrix and/or a set of signal routing orswitching elements that facilitate the application, delivery, and/orrouting of stimulation signals to one or more sets of electrodeassemblies, electrical contacts, and/or signal transfer devices at anygiven time. In one embodiment, the switching unit 110 c may facilitatethe electrical activation of particular electrode assemblies, contacts,and/or signal transfer devices, possibly while other such elementsremain electrically inactive or electrically float.

The switching unit 110 c may additionally or alternatively facilitatethe simultaneous or nearly simultaneous activation of different sets ofelectrode assemblies, contacts, and/or signal transfer devices inaccordance with different stimulation parameter sets, possibly while oneor more sets of electrode assemblies, contacts, and/or signal transferdevices remain electrically inactive. For example, the switching unit110 c may route a first set of stimulation signals characterized by apeak current amplitude of 3 mA to a first set of electrical contacts 160carried by an electrode assembly 150, while routing a second set ofstimulation signals characterized by a peak current amplitude of 6 mA toa second set of electrical contacts carried by the same or a differentelectrode assembly 150. As another example, the switching unit 110 c mayroute a set of unipolar stimulation signals characterized by a peakamplitude of 4.5 mA and an aperiodic pulse repetition frequency to afirst set of electrode assemblies, while routing a set of bipolarstimulation signals characterized by a peak amplitude of 7.5 mA and a 50Hertz pulse repetition frequency to a second set of electrodeassemblies. Depending upon embodiment details, such selective and/orsimultaneous electrical activation may be facilitated with 1) a pulsegenerating unit 110 b configured to simultaneously generate and/oroutput different sets or versions of stimulation signals; 2) a dual IPGsystem; and/or 3) an IPG 100 that includes more than one pulsegenerating unit 110 b.

FIG. 2B is an internal block diagram of a stimulation signal generatoror IPG 101 according to another embodiment of the invention. Relative toFIG. 2A, like reference numbers may indicate like or analogous elements.In one embodiment, the IPG 101 comprises multiple pulse generating units110 b 1, 110 b 2 and multiple outputs 104 a, 104 b. An IPG 101 of thetype shown in FIG. 2B may be coupled to two or more electrode assemblies150 to facilitate the stimulation of different target neural populationsin one or more manners, which may depend upon the nature or extent of apatient's neurologic dysfunction and/or embodiment details. Thedifferent target neural populations may reside in a variety ofanatomical locations. For example, a first and a second target neuralpopulation may reside a) in the same or different brain hemispheres; b)in the brain and in the spinal cord; c) at a central nervous systemlocation and at a peripheral nervous system location; or d) at differentperipheral nervous system locations. An IPG 101 having multiple pulsegenerating units 110 b 1, 110 b 2 may stimulate different neuralpopulations simultaneously or separately, in an independent orcorrelated manner. One or both pulse generating units 110 b 1, 110 b 2may generate stimulation signals in various manners described herein tofacilitate reduced power consumption and/or improved or maintainedneural stimulation efficacy.

FIG. 6 is a block diagram illustrating particular communication modesthat may be supported by a neural stimulation system 1000 according toan embodiment of the invention. In one embodiment, thetelemetry/communication unit 110 a may provide two-way communication forreceiving signals from and transmitting signals to an externalprogrammer 180. The telemetry/communication unit 110 a may include awire-based and/or wireless telemetry interface that employs magnetic,radio frequency (RF), optical, and/or other signaling techniques tocommunicate with the programmer 180. Passwords, handshakes, and paritychecks can be employed for signal integrity and/or security purposes.The telemetry/communication unit 110 a may additionally or alternativelyinclude one or more wire-based and/or wireless interfaces thatfacilitate communication with another device such as a patientmonitoring unit 200 or a computer (not shown).

In one embodiment, the programmer 180 may comprise a portable electronicdevice, such as but not limited to a personal digital assistant (PDA) orother type of computing device configured as an interface forcommunicating with the IPG 100. Such communication may involve thetransfer or exchange of control signals, commands, configuration data,instructions, timing or time-base reference information, and/or otherinformation by way of the communication unit 110 a. In certainembodiments, the programmer 180 may additionally comprise a programmingwand that facilitates telemetric communication with the IPG 100, in amanner understood by those skilled in the art.

The programmer 180 may also comprise and/or be configured forcommunication with one or more programmable computer media (PCM) 185. Invarious embodiments, a PCM 185 may comprise a memory and/or one or moreother types of data storage devices. The PCM 185 may store stimulationsignal definition information and/or treatment program information. Incertain embodiments, the PCM 185 comprises a database that may includepatient data, statistical information, and/or one or more types oftreatment program information for one or more patients. This databasemay include stimulation waveform information corresponding tostimulation signal frequencies, durations, amplitudes, locations, andthe like, and possibly measurement or monitoring results generated by apatient monitoring unit 200.

The programmer 180 may be operated by a physician, clinician, ortherapist to communicate a set of neural stimulation parameters and/orassociated information to the IPG 100. Programming capabilities mayinclude the ability to specify and/or modify various waveform parametersand/or functions corresponding to a pulse generating unit 110 b.Programming capabilities may further include an ability to performdiagnostics and/or store and/or retrieve telemetered data. It is to beappreciated by those of ordinary skill in the art that the IPG 100 canbe programmed using a personal or other type of computer (not shown)employing appropriate software and a programming wand (not shown).

Adjusting or Affecting Power Consumption and/or Efficacy

In accordance with various embodiments of the present invention, powerconsumption may be improved or decreased and/or neural stimulationefficacy increased, preserved, or generally maintained by controlling,adjusting, modifying, and/or modulating a manner in which neuralstimulation is applied or delivered to a patient. As indicated above,particular systems and/or methods described herein may apply or deliverneural stimulation at one or more subthreshold and/or suprathresholdamplitudes, levels, or intensities at one or more times. A subthresholdstimulation amplitude may correspond to a particular fraction orpercentage of a lowest or near lowest test stimulation signal amplitudeat which a patient exhibits a particular type of response. The responsemay correspond to an externally measurable or observable reaction suchas a movement; an effect upon an internally measurable or observablesignal such as an EEG signal; a patient-reported sensation; and/oranother type of response.

Various systems and/or methods described herein may apply or deliverbipolar and/or unipolar, monopolar, or isopolar stimulation signals.Unipolar stimulation signals exhibit an identical polarity at any giventime, and electrical continuity may be provided by a current return pathor return electrode that is remotely positioned relative to a targetneural population. Unipolar stimulation may potentially reduce powerconsumption, provide enhanced efficacy or efficiency stimulation, and/ormitigate collateral effects. Depending upon embodiment details, certainsystems and/or methods may apply or deliver unipolar stimulation at onetime and bipolar stimulation at another time. Some embodiments mayprovide unipolar stimulation one or more manners that are identical,essentially identical, or analogous to those described in U.S.application Ser. No. 10/910,775, previously incorporated herein byreference.

In certain embodiments, a neural stimulation system 1000 may beinitially configured to provide or deliver optimum, near-optimum, orexpected best stimulation to a patient relative to one or more patientstates, symptoms, and/or functional deficits under consideration at aparticular time. That is, a neural stimulation system 1000 may beconfigured to provide stimulation in a manner determined or expected tobe most efficacious, most therapeutic, efficacious, or therapeutic. Suchstimulation may correspond to an initial stimulation configuration.

A neural stimulation system 1000 may be subsequently configured oradjusted to provide or deliver effective, generally effective, adequate,acceptable, and/or sufficient stimulation at a reduced power level toone or more target neural populations relative to a set of patientstates, conditions, symptoms, and/or functional deficits underconsideration. A neural stimulation system 1000 may additionally oralternatively be configured to provide changing, varying, orneurologically novel or generally novel stimulation signals to one ormore target neural populations in order to maintain or improve neuralstimulation efficacy. Stimulation provided in the aforementioned mannersmay address, treat, and/or relieve one or more patient conditions,symptoms, and/or functional deficits in a manner that is similar oridentical to or possibly better than stimulation provided in accordancewith an initial stimulation configuration, and may correspond to anadjusted stimulation configuration. An adjusted stimulationconfiguration provided in accordance with various embodiments of theinvention may extend battery life and/or a power source recharginginterval, and/or improve, sustain, or generally maintain neuralstimulation efficacy. To facilitate prolonged battery life or extendpower source recharging intervals, various embodiments may apply neuralstimulation in accordance with an adjusted stimulation configurationwhen a battery and/or other power source is essentially fully-charged,or prior to the occurrence of noticeable, moderate, appreciable, orsignificant power source depletion.

Depending upon embodiment details, power consumption and/or efficacy mayaffected by adjusting or varying one or more parameters associated witha treatment program. In several embodiments, such parameters maycorrespond to one or more neural stimulation procedures. A neuralstimulation procedure may define, specify, and/or indicate one or moresets of stimulation period parameters, stimulation waveform parameters,stimulation modulation parameters, and/or stimulation locationparameters. Stimulation period parameters may specify or indicate one ormore active periods during which stimulation signals may be applied to apatient, and/or one or more quiescent periods during which neuralstimulation may be avoided. Stimulation period parameters may correspondto subseconds-based, seconds-based, hours-based, and/or other timedomains or scales.

Stimulation waveform parameters may define, describe, or characterize astimulation signal in a manner identical, essentially identical,analogous, or generally analogous to that described above with respectto FIG. 3. In general, stimulation waveform parameters may define ordescribe a stimulation signal on a subseconds-based time domain, and/orpossibly a seconds-based time domain.

Stimulation modulation parameters may define, specify, or indicate oneor more manners of modulating or transforming neural stimulationsignals. Depending upon embodiment details, stimulation modulationparameters may correspond to one or more mathematical operations orfunctions applied to particular stimulation signal parameters, possiblyrelative to one or more time scales. Stimulation modulation parametersmay typically correspond to subseconds-based, seconds-based,hours-based, and/or other time domains.

Finally, stimulation location parameters may define or specifyparticular sets of signal transfer devices, electrode structures,electrode assemblies, and/or conductive elements to which stimulationsignals may be applied or directed at one or more times.

Duty Cycle Modification

In various embodiments, power consumption may be decreased and/or neuralstimulation efficacy maintained or increased by controlling, adjusting,or modifying a neural stimulation duty cycle. Duty cycle may be definedas a percentage of time a device is “ON,” consuming power, or depletinga power source during or relative to a time domain under consideration.Various types of time domains may be defined, including an hours-basedtime domain, a seconds-based time domain, and a subseconds-based timedomain as indicated above. Thus, in one embodiment, duty cycle may bedefined asDuty Cycle=(time on)/(time on+time off)relative to a given type of time domain.

In certain embodiments, instead of enabling, allowing, or providing forstimulation pulse or pulse train generation or delivery during an entiretime domain in a continuous or uninterrupted manner, a neural stimulatorsuch as an IPG 100 or particular elements therein (e.g., a pulsegenerator 108) may be selectively turned off or disabled during one ormore portions or segments of one or more time domains underconsideration. This reduces a neural stimulation duty cycle, therebyconserving power. In further aspects of these embodiments, a givenseries of electromagnetic stimulation signals may be interrupted and astimulation parameter selected/adjusted to conserve power. Theinterruption and/or parameter selection/adjustment can occur well beforethe power provided to the pulse generator (e.g., by a battery) issignificantly depleted, to provide a significant decrease in powerconsumption.

FIG. 7A is a graph illustrating an exemplary interruption, disabling, orcessation of stimulation signal generation relative to an hours-basedtime domain to effectuate a reduction in an hours-based duty cycleaccording to an embodiment of the invention. In accordance with FIG. 7A,a neural stimulator or particular elements therein may be configured inan “ON” state or enabled during a first hours-based time period T_(H1),and configured in an “OFF” state or disabled during a second hours-basedtime period T_(H2). The combined duration of T_(H1) and T_(H2) form anhours-based time domain T_(H) under consideration. In an exemplaryembodiment, T_(H1) may be 18 hours, and T_(H2) may be 6 hours. T_(H1)may have a significant likelihood of corresponding to hours during whicha patient is expected to be awake, and T_(H2) may have a significantlikelihood of corresponding to hours during which a patient is expectedto be asleep. Such an operational scheme may be useful for patientssuffering from movement disorders such as essential tremor orParkinson's Disease because patient symptoms may be less severe duringslumber.

In the foregoing example, a six-hour off time per day would result inDuty Cycle_(H)=18/(18+6)=0.75or a 75% hours-based duty cycle. In other words, a six-hour off timeresults in a 25% hours-based duty cycle reduction, thereby conservingpower.

T_(H2) may be a portion or fraction of T_(H) that meets a reduced dutycycle target in view of an acceptable level of clinical efficacy. Ingeneral, T_(H) may be comprised of multiple “ON” times and one or more“OFF” times (e.g., there may be a T_(H3) that corresponds to an “ON”time, a T_(H4) that corresponds to an “OFF” time, etc . . . ). Theduration of one or more “ON” and/or “OFF” times may be determined,established, programmably specified, and/or adjusted in a periodic,aperiodic, or random manner, possibly accordance with a target dutycycle relative to a given degree of clinical efficacy. In FIG. 7A, anhours-based time domain corresponds to a 24-hour period. One or moreother types of hours-based time domains may be defined depending uponembodiment details, actual or expected patient state, and/or clinicialconditions.

FIG. 7B is a graph illustrating an exemplary interruption, disabling, orcessation of stimulation signal generation in a seconds-based timedomain to effectuate a reduction in a seconds-based duty cycle accordingto an embodiment of the invention. In accordance with FIG. 7B, a neuralstimulator or particular elements therein may be configured in an “ON”state or enabled during a first seconds-based time period T_(S1), andconfigured in an “OFF” state or disabled during a second seconds-basedtime period T_(S2). The combined duration of T_(S1) and T_(S2) form aseconds-based time domain T_(S) under consideration. In an exemplaryembodiment, T_(S1) may be 20 seconds, and T_(S2) may be 5 seconds. Thus,if neural stimulation comprises the periodic or quasi-periodicapplication of stimulation signals or a pulse train for 20 secondsfollowed by a quiescent interval of 5 seconds, a seconds-based dutycycle may be defined asDuty Cycle_(s)=20/(20+5)=0.80giving 80% seconds-based duty cycle, which provides a 20% seconds-basedduty cycle reduction.

T_(S2) may be a portion or fraction of T_(S) that meets a reduced dutycycle target in view of an acceptable level of clinical efficacy. Ingeneral, T_(S) may be comprised of multiple “ON” times and one or more“OFF” times (e.g., there may be a T_(S3) that corresponds to an “ON”time, a T_(S4) that corresponds to an “OFF” time, etc . . . ). Theduration of one or more “OFF” times may be determined, established,programmably specified, and/or adjusted in accordance with a target dutycycle relative to a given degree of clinical efficacy. In certainembodiments, T_(S2) and/or one or more other “OFF” times may bedetermined in a random, quasi-random, or aperiodic manner, possibly withrespect to a minimum duration T_(S1) or total “ON” time within T_(S).

FIG. 7C is a graph illustrating an exemplary interruption, disabling, orcessation of stimulation signal generation in a subseconds-based timedomain to effectuate a reduction in a subseconds-based or seconds-basedduty cycle according to an embodiment of the invention. In certainembodiments, a subseconds-based duty cycle may be reduced by omitting orskipping one or more pulses within a pulse train (indicated in FIG. 7Cby cross hatching) during a subseconds-based or seconds-based timeinterval, possibly on a periodic, aperiodic, or quasi-random basis. Inthe embodiment shown in FIG. 7C, four pulses are delivered and a fifthpulse is skipped on a periodic basis. That is, a number of deliveredpulses PD equals four, and a number of skipped pulses Ps equals one.This results in a subseconds-based duty cycle ofDuty Cycle_(SS)=4/(4+1)=0.80or an 80% subseconds-based duty cycle, thereby providing a 20%subseconds-based duty cycle reduction. Depending upon embodimentdetails, a number of pulses skipped within or relative to a givensubseconds-based or seconds-based time interval may be greater than one,possibly based upon a target subseconds-based duty cycle in view of anacceptable degree of clinical efficacy.

In certain embodiments, a neural stimulation duty cycle may be furtherreduced through duty cycle reductions in two or more time domains. Anoverall or effective duty cycle may be given by a product of individualduty cycles in the time domains under consideration. For example,combining the exemplary duty cycle reductions described above withrespect to FIGS. 7A-7C gives rise to an effective duty cycle ofDuty Cycle_(EFF)=(DC _(H))(DC _(S))(DC _(SS))=(0.75)(0.80)(0.80)=0.48or a 48% effective duty cycle, which provides a 52% overall duty cyclereduction. Such a duty cycle reduction may significantly prolong batterylife. Depending upon embodiment details, duty cycle reductionsassociated with essentially any plurality of time domains (e.g., aseconds-based time domain and a subseconds-based time domain; anhours-based time domain and a seconds-based time domain; or anhours-based time-domain and a subseconds-based time domain) may becombined in a manner identical or analogous to that described above

Various other types of duty cycle variation or modification may berelevant depending upon embodiment details, the nature of a patient'sneurologic dysfunction, and/or short-term or long-term patient responseto neural stimulation. For a patient experiencing a movement disordersuch as essential tremor, an amount of time a patient continues toexperience symptomatic benefit during an OFF time may depend upon acumulative or aggregate duration of recent ON times. As stimulation isapplied over the course of more ON times, at least some symptomaticbenefit may persist across a longer OFF time.

As a representative example, stimulation may be initially applied inaccordance with a 5 minute ON time and a 2 minute OFF time. At each 30minute interval after stimulation begins, the OFF time may be increasedby 1 minute while the ON time may be maintained at 5 minutes, untilreaching an OFF time of 5 minutes. Then, at each 1 hour interval afteran ON/OFF duty cycle of 5 minutes/5 minutes is reached, the OFF time maybe increased by 1 minute until reaching an OFF time of 10 minutes. Oneor more of the preceding time intervals may differ in length as a resultof patient-specific factors.

In other representative examples, ON times may also be varied instead ofor in addition to OFF times. Additionally or alternatively, particularON and/or OFF times may be adjusted or limited based upon themeasurement of a patient-specific parameter such as a tremor frequency(e.g., using accelerometers). Such adjustment may occur manually, orautomatically using a closed-loop system.

Modification of Stimulation Frequency Characteristics

In various embodiments, power consumption may be decreased and/or neuralstimulation efficacy affected by adjusting or modifying one or moretypes of stimulation frequency characteristics, possibly relative to oneor more time domains under consideration. Depending upon embodimentdetails, modification of stimulation frequency characteristics mayresult in or correspond to a duty cycle modification. As a result,particular considerations described above may identically, analogously,or similarly apply to one or more embodiments described hereafter.

In certain embodiments, power consumption may be reduced and/or neuralstimulation efficacy affected at one or more times through theapplication or delivery of stimulation signals characterized inaccordance with one or more types of naturally or intrinsicallyoccurring neural signaling patterns. For example, the application ordelivery of stimulation signals to a set of target neural populationsmay be timed or approximately timed based upon one or more knowncortical ensemble discharge frequency ranges or bands. Cortical ensembledischarge frequency bands are typically categorized as delta, theta,alpha, beta, and gamma frequency bands. In general, the delta frequencyband corresponds to frequencies less than approximately 4 Hz; the thetafrequency band corresponds to frequencies between approximately 4 Hz andapproximately 8 Hz; the alpha frequency band corresponds to frequenciesbetween approximately 8 Hz and 13 Hz; the beta frequency bandcorresponds to frequencies between approximately 13 Hz and 30 Hz; andthe gamma frequency band corresponds to frequencies greater thanapproximately 30 Hz. Those skilled in the art will understand that theabove frequency band delineations are approximate (e.g., alphafrequencies may be alternately defined as falling between approximately3.0 or 3.5 Hz and 7.0, 7.5, or possibly even 10.0 Hz).

In various embodiments, stimulation signals that are generated, applied,or delivered in a manner that corresponds to an intrinsic neuralsignaling behavior may include or comprise a set or series of pulsebursts or pulse packets. An actual, average, or estimated number ofpulse bursts or pulse packets generated, applied, or delivered persecond may correspond or approximately correspond to a particular typeof intrinsic neural signaling behavior, such as a delta, theta, alpha,beta, or gamma frequency.

A number of pulse bursts per second may be defined as an interburstfrequency. In several embodiments, pulse bursts are temporally separatedby a quiescent interval. In some embodiments, one or more pulse burstsmay be temporally separated by nearly or approximately quiescentintervals, during which a set of additional, possibly reduced-amplitudeand/or less frequent stimulation signals may be applied in apredetermined, pseudo-random, and/or aperiodic manner.

Depending upon embodiment details, an individual pulse burst or packetmay comprise a set of pulses characterized by an actual, average, orestimated intraburst or intrapacket pulse repetition frequency, forexample, an intraburst pulse repetition frequency between approximately50 Hz and 500 Hz. In one embodiment, intraburst pulse repetitionfrequency may vary with time and/or packet count in a predetermined,quasi-random, or aperiodic manner.

Herein, neural stimulation that comprises a set of pulse bursts appliedin a manner that corresponds to one or more types of intrinsic neuralsignaling behavior is defined as neuro-burst stimulation. Thus, relativeto the aforementioned cortical ensemble discharge frequency bands,neuro-burst stimulation provided by various embodiments of the inventionmay include delta-burst, theta-burst, alpha-burst, beta-burst, and/orgamma-burst stimulation. Depending upon a patient's neurologic profileand/or embodiment details, neuro-burst stimulation may be applied and/ordelivered to one or more target neural populations at one or more timeson a continuous, quasi-continuous, periodic, quasi-random, or aperiodicbasis, possibly in association with other types of stimulation signals.

Neuro-burst stimulation may be generated or applied at one or moreamplitudes, levels, or intensities that correspond tosubthreshold-level, threshold-level, and/or suprathreshold-levelstimulation. Such amplitudes may remain constant, or vary from or withina given burst to another burst. In some embodiments, one or moreintraburst stimulation parameters (e.g., intraburst pulse amplitude,intraburst frequency, and/or intraburst first-phase pulse width) mayvary across a series of pulse bursts. Such variation may occur in apredetermined, quasi-random, and/or aperiodic (e.g., chaotic) manner.

One or more types of neuro-burst stimulation may facilitate enhancedneural stimulation efficacy and/or reduced power consumption. Forexample, theta-burst stimulation may facilitate enhanced functionalrecovery or development in patients experiencing neurologic dysfunctionassociated with stroke, TBI, learning and/or memory disorders,Alzheimer's disease, and/or other conditions. Theta-burst stimulationmay facilitate neurological consolidation of newly or recently acquiredfunctional gains, learned skills, and/or memories, possibly through oneor more mechanisms corresponding or related to LTP, depotentiation, LTD,and/or synaptic plasticity. Moreover, theta-burst and/or one or moreother types of neuro-burst stimulation may facilitate enhancedsymptomatic relief associated with neurologic conditions involvingmaladaptive neuroplasticity, for example, tinnitus, auditoryhallucinations, phantom limb pain or other chronic pain syndromes,and/or other conditions.

Representative manners in which theta-burst stimulation may affectneurologic processes are described in a) “Induction and Reversal ofLong-Term Potentiation by Low- and High-Intensity Theta PatternStimulation,” S. Barr et al., The Journal of Neuroscience, July 1995,15(7): 5402-5410; b) “Reversal of LEP by Theta Frequency Stimulation,”John Larson et al., Brain Research, 600(1993) 97-102; and c)“Theta-burst Stimulation of the Human Motor Cortex,” Ying-Zu Huang etal., Neuron, Vol. 45, 201-206, Jan. 20, 2005, each of which isincorporated herein by reference.

One or more types of neuro-burst stimulation (e.g., gamma-burststimulation) may facilitate an interruption, disruption, shifting,modulation, desynchronization, and/or other type of alteration (e.g.,the establishment of or a change in a neural entrainment pattern) ofdysfunctional or undesired neural signaling behavior (e.g., oscillatorybehavior and/or one or more types of neural signal coherence associatedwith a movement disorder). Such neuro-burst stimulation may involvesubthreshold-level, near-threshold-level, threshold-level, and/orsuprathreshold-level stimulation signals, where individual pulses orpulse packets corresponding to threshshold-level or suprathreshold-levelstimulation may be brief, relatively brief, generally infrequent, and/orintermittent relative to subthreshold-level pulses or pulse packets.

FIG. 8A is a graph illustrating an exemplary theta-burst stimulationpattern that may affect power consumption and/or neural stimulationefficacy according to an embodiment of the invention. In one embodiment,a theta-burst stimulation pattern may comprise 4 pulse bursts or packetsper second, where each pulse packet comprises ten pulses characterizedby an intrapacket pulse repetition frequency of 200 Hertz. Thus, eachpulse packet comprises ten 200 Hz pulses, and a temporal reference pointcorresponding to any given pulse packet is separated from an equivalentreference point corresponding to a subsequent pulse packet by 200 ms.

Additional and/or alternate types of neural stimulation frequencymodification may reduce power consumption and/or affect neuralstimulation efficacy. FIG. 8B is a graph illustrating an exemplarystimulation frequency modification relative to an hours-based timedomain T_(H) to affect power consumption and/or neural stimulationefficacy according to an embodiment of the invention. In FIG. 8B, neuralstimulation characterized by a first set of stimulation frequencycharacteristics f₁ may be applied to a patient during a firsthours-based time period T_(H1). Following T_(H1), neural stimulationcharacterized by a second set of stimulation frequency characteristicsf₂ may be applied to the patient during a second hours-based time periodT_(H2). Certain embodiments may include a transition period T_(TRANS)between T_(H1) and T_(H2) and/or T_(H2) and T_(H1), wherein neuralstimulation frequency characteristics are varied in a smooth, gradual,or generally gradual manner between f₁ and f₂. The transition period maycorrespond to a transition frequency function or envelope fTRANS, whichmay comprise, for example, a linear or polynomial based change infrequency versus time.

Depending upon embodiment details, the first set of stimulationfrequency characteristics f₁ may correspond to a stimulation signalfrequency, frequency pattern, and/or frequency function that has beendetermined or is expected to be most effective, effective, or generallyeffective for treating one or more patient symptoms and/or facilitatingone or more neurofunctional and/or patient outcomes. For example, f₁ mayspecify a 30 Hz or other pulse repetition frequency. The second set ofstimulation frequency characteristics f₂ may correspond to a reducedstimulation signal frequency, frequency pattern, and/or frequencyfunction that may be effective, generally effective, or adequate fortreating one or more patient symptoms and/or facilitating particularpatient outcomes. For example, f₂ may correspond to a 20 Hz or otherpulse repetition frequency. In an exemplary embodiment in which T_(H1)equals 18 hours, f₁ equals 30 Hz, T_(H2) equals 6 hours, and f₂ equals20 Hz, power consumption during T_(H2) may be reduced by approximately33% relative to that during T_(H1). In the event that T_(H2) correspondsto hours during which a patient is likely to be asleep or resting,patient symptoms may be less severe, and hence a lower pulse repetitionfrequency may be appropriate.

In an alternate embodiment, f₁ and/or f₂ may define, specify, orindicate one or more neuro-burst stimulation patterns. In one exemplaryembodiment, f₁ may correspond to a 50 Hz pulse repetition frequencyduring an 18 hour T_(H1) period. During a 6 hour T_(H2) period, f₂ maycorrespond to a theta-burst pattern, for example, 5 pulse packets persecond, where each pulse packet comprises five 100 Hz pulses. In such anembodiment, power consumption during T_(H2) may be reduced relative tothat during T_(H1) by approximately 50% under equi-amplitude conditions.

An hours-based time domain may comprise other or multiple time periodscharacterized by modified (e.g., reduced, increased, and/or varying)frequency stimulation. Stimulation frequency characteristics mayalternatively or additionally be modified before, during, and/or afterone or more time periods corresponding to an adjunctive or synergistictherapy. An adjunctive therapy may comprise, for example, a drugtherapy, a neurotrophic and/or growth factor therapy, and/or abehavioral therapy. Depending upon embodiment details, a behavioraltherapy that is relevant to one or more types of neural stimulation inaccordance with the present invention may comprise a physical therapyactivity, a movement and/or balance exercise, a strength trainingactivity, an activity of daily living (ADL), a vision exercise, areading task, a speech task, a memory or concentration task, avisualization or imagination exercise, an auditory activity, anolfactory activity, a biofeedback activity, and/or another type ofbehavior, task, or activity that may be relevant to a patient'sfunctional state, development, and/or recovery.

In one embodiment, one or more types of neuro-burst stimulation may beapplied to a patient before, during, and/or after a behavioral therapysession. In an exemplary embodiment, during a behavioral therapy periodT_(BT) that may range between approximately one-half hour and several(e.g., four) hours, one or more periods or intervals characterized bytheta-burst and/or other neuro-burst stimulation that is identical,essentially identical, or similar to or different from that describedabove may be applied to the patient. Outside T_(BT), neural stimulationmay be avoided, or applied to the patient in a variety of manners,including one or more manners described herein.

In various embodiments, stimulation frequency characteristics mayalternatively or additionally be varied, modified, or modulated relativeto a seconds-based and/or a subseconds-based time domain. FIG. 8C is agraph illustrating an exemplary stimulation frequency modificationrelative to a seconds-based time domain T_(S) to power consumptionand/or neural stimulation efficacy according to an embodiment of theinvention. In one embodiment, neural stimulation characterized by afirst set of stimulation frequency characteristics f₁ (e.g., a pulserepetition frequency of 30 Hz) may be applied to a patient during afirst seconds-based time period T_(S1) (e.g., 15 seconds). Neuralstimulation characterized by a second set of stimulation frequencycharacteristics f₂ (e.g., a pulse repetition frequency of 20 Hz) may beapplied to the patient during a second seconds-based time period T_(S2)(e.g., 5 seconds). In such an embodiment, power consumed during T_(S2)may be reduced relative to that during T_(S1) by a factor ofapproximately 33%, which may reduce overall power consumption byapproximately 8.3%.

Depending upon embodiment details, the first set of stimulationfrequency characteristics f₁ may correspond to a stimulation signalfrequency, frequency pattern, and/or frequency function that has beendetermined or is expected to be most effective or effective for treatingone or more patient symptoms and/or facilitating one or more patientoutcomes. The second set of stimulation frequency characteristics f₂ maycorrespond to a reduced stimulation signal frequency, frequency pattern,and/or frequency function that may be effective, generally effective, oradequate for treating one or more patient symptoms and/or facilitatingparticular patient outcomes. In certain embodiments, f₁ and/or f₂ maycorrespond to neuro-burst stimulation. From a given seconds-based timedomain Ts to another, some embodiments may establish f₂ in a variable,quasi-random, or aperiodic manner, possibly relative to a maximum and/orminimum acceptable f₂.

In general, the duration of T_(S2) may be established or determined in amanner that meets or approximately meets a power consumption target inview of an acceptable level of clinical efficacy. In certainembodiments, a seconds-based time domain T_(S) may comprise other ormultiple periods characterized by reduced frequency neural stimulation.The total duration of such periods may be determined in a random,quasi-random, or aperiodic manner, possibly with respect to a minimumduration T_(S1) and/or minimum level of clinical efficacy.

In some embodiments, stimulation frequency characteristics may vary inaccordance with a time dependent function f(t), for example, a sinusoid.In one embodiment, a maximum frequency f_(max) may correspond to afrequency determined or expected to be most effective or effectivefrequency for treating one or more patient symptoms. A minimum frequencyfmin may correspond to a lowest frequency suitable for adequatelytreating one or more patient symptoms. In general, f(t) may comprise afunction bounded by f_(max) and f_(min). Furthermore, f(t) may becharacterized by an average or RMS frequency that may be effective,generally effective, or adequate for treating a set of patient symptoms.

FIG. 8D is a graph illustrating an exemplary stimulation frequencyfunction applied in a seconds-based time domain to effectuate areduction in power consumption according to an embodiment of theinvention. In one embodiment, f(t) comprises a sinusoidal frequencyfunction that varies between an f_(max) pulse repetition frequency of 50Hz and an f_(min) pulse repetition frequency of 20 Hz. Stimulation inaccordance with such a function may result in an average pulserepetition frequency of 35 Hz, which may maintain or improve neuralstimulation efficacy and/or reduce power consumption by approximately30%. In other embodiments, f(t) may comprise another type of function(e.g., a square wave or a triangle wave) and/or a function that isskewed or weighted relative to a particular frequency target.

In some embodiments, stimulation signal frequency may be modifiedrelative to a subseconds-based time domain in accordance with adiscretized linear or nonlinear frequency chirp pattern or function.FIG. 8E is a graph illustrating an exemplary discretized frequency chirppattern according to an embodiment of the invention. In one embodiment,a frequency chirp pattern corresponds to a series of pulse packetsacross and/or within which pulse repetition frequency decreases and/orincreases with time or pulse count. For example, each pulse packet maycomprise a plurality of biphasic or polyphasic pulses, where an amountof time elapsed between different pulses as referenced with respect tomatching pulse phase reference points increases or decreases from onepulse to the next. In another embodiment, a degree, extent, or magnitudeof chirping may differ from a given pulse packet to another; and/orchirped pulse packets may be separated by or interspersed withnon-chirped pulse packets.

Modification of Stimulation Amplitude Characteristics

In various embodiments, power consumption and/or neural stimulationefficacy may be affected by modifying one or more stimulation amplitudecharacteristics (e.g., a peak current and/or a peak voltage level)relative to one or more time domains under consideration. In variousembodiments, stimulation amplitude characteristics may be variedrelative to an hours-based time domain, a seconds-based time domain, asubseconds-based time domain, and/or another type of time domain.

In one embodiment, neural stimulation efficacy may be sustained orimproved through the application or delivery of one or moresuprathreshold or near-suprathreshold pulses or bursts during a neuralstimulation procedure that is primarily characterized by subthresholdstimulation. Such suprathreshold pulses or bursts may occur in apredetermined, aperiodic, or random manner. For example, during asubthreshold stimulation procedure that applies stimulation signals at acurrent level corresponding to 50% of a movement, EMG, or sensationthreshold, a threshold-level or suprathreshold-level pulse or pulse setmay be applied at a current level corresponding to 100%, 105%, or 110%of such a threshold once every 3 minutes, or at random or aperiodictimes that fall between a minimum and a maximum allowable duration timeperiod.

FIG. 9A is a graph illustrating an exemplary stimulation signal level,amplitude, or magnitude adjustment relative to an hours-based timedomain T_(H) to affect power consumption and/or neural stimulationefficacy according to an embodiment of the invention. In someembodiments, during a first time hours-based period T_(H1), astimulation signal may have an amplitude A₁ that may treat one or morepatient symptoms in a most effective, expected most effective, oreffective manner. During a second hours-based time period T_(H2), astimulation signal may have a reduced amplitude A₂ that may treat one ormore patient symptoms in an effective, generally effective, or adequatemanner. Certain embodiments may include a transition period T_(TRANS)between T_(H1) and T_(H2) and/or T_(H2) and T_(H1), wherein neuralstimulation amplitude characteristics are varied in a smooth, gradual,or generally gradual manner between A₁ and A₂. The transition period maycorrespond to a transition amplitude function or envelope A_(TRANS),which may comprise, for example, a linear or polynomial based change inamplitude versus time.

Depending upon embodiment details, A₂ may range from approximately 5% to95% of A₁. In certain embodiments, A₂ may be a function of time,possibly varying in a predetermined, quasi-random, or aperiodic manner.Reduced amplitude stimulation may be appropriate, for example, duringtimes that a patient is expected to be asleep or resting. In the eventT₁ equals approximately 18 hours, T₂ equals approximately 6 hours, andA₁ is approximately 50% of A₂, power consumption may be reduced byapproximately 12.5% relative to ongoing stimulation characterized byamplitude A₁.

FIG. 9B is a graph illustrating an exemplary stimulation signalamplitude adjustment or modification relative to a seconds-based timedomain T_(S) to affect power consumption and/or neural stimulationefficacy according to an embodiment of the invention. In someembodiments, during a first seconds-based time period T_(S1), forexample, 20 seconds, a stimulation signal may have an amplitude A₁ thatmay treat one or more patient symptoms in a most effective, expectedmost effective, or effective manner. During a second time period T_(S2),for example, 10 seconds, a stimulation signal may have a reducedamplitude A₂ that may treat one or more patient symptoms in aneffective, generally effective, or adequate manner. Depending uponembodiment details, A₂ may range from approximately 5% to 95% of A₁. Inthe event that T_(S1) equals approximately 20 seconds, T_(S2) equalsapproximately 10 seconds, and A₂ is approximately 25% of A₁, powerconsumption may be reduced by approximately 7.5% relative to ongoingstimulation characterized by amplitude A₁. In certain embodiments, aseconds-based time domain T_(S) may comprise other and/or multiplereduced amplitude time periods. Additionally or alternatively, anamplitude reduction may be determined in a variable, quasi-random, oraperiodic manner, possibly relative to a minimum and/or maximumamplitude reduction and/or an acceptable level of clinical efficacy.

FIG. 9C is a graph illustrating an exemplary stimulation signalamplitude adjustment or modification relative to a subseconds-based timedomain T_(SS) to affect power consumption and/or neural stimulationefficacy according to an embodiment of the invention. In one embodiment,a first number of pulses P₁ may have an amplitude or average amplitudeA₁ that is determined or expected to be most effective, effective, orgenerally effective for treating one or more patient symptoms. Invarious embodiments, amplitude A₁ corresponds to subthreshold-levelstimulation, for example, a given percentage (e.g., between 25% and 75%)of a movement or EMG threshold. A second number of pulses P₂ may haveone or more amplitudes A_(2A), A_(2B) determined or expected to beeffective, generally effective, or adequate for treating one or morepatient symptoms. In an exemplary embodiment in which P₁ equals 6, P₂equals 2, A_(2A) is approximately 50% of A₁, and A_(2B) is approximately25% of A₁, power consumption may be reduced by approximately 15.625%. Ingeneral, a number of reduced amplitude pulses and/or the amplitudesassociated therewith with may depend upon embodiment details, and maydepend upon a reduced power consumption target in view of an acceptablelevel of clinical efficacy.

In one embodiment, neural stimulation efficacy may be maintained orimproved through the application or delivery of one or moresuprathreshold-level or near-suprathreshold-level pulses or bursts inassociation with a neural stimulation procedure that includes or isprimarily characterized by subthreshold-level stimulation, for example,in a manner indicated in FIG. 9C. Such suprathreshold-level pulses orbursts may occur in a predetermined, aperiodic, or random manner. Forexample, during a subthreshold-level stimulation procedure that appliesstimulation signals at a current level corresponding to 50% of amovement, EMG, or sensation threshold, a suprathreshold-level pulse orpulse set may be applied at a current level corresponding toapproximately 100% of such a threshold once every j seconds, twice everyk minutes, or at random times that fall between a minimum and a maximumallowable length time period. While FIG. 9C depicts a singlethreshold-level or suprathreshold-level pulse, in various embodimentsneural stimulation may involve additional threshold-level and/orsuprathreshold-level pulses, where at least some of such pulses may havedifferent peak amplitudes.

From a patient treatment perspective, the effect(s) associated with anamplitude variation may be identical, essentially identical, analogous,similar, or generally similar to the effect(s) associated with a dutycycle variation and/or a pulse repetition frequency variation in view ofan amount of electric charge delivered during a specific pulse phase orpulse subinterval.

Stimulation Intensity Modification

A neurostimulator may be viewed as a device capable of imparting energyto one or more neural populations in a controllable and/or therapeuticmanner. Such energy may comprise electrical and/or magnetic stimulationsignals that may influence, affect, or alter neural membrane potentials.As described above, stimulation signals may comprise a set or series ofpulses or pulse trains. In certain embodiments, an extent or averageextent to which neural stimulation affects neural tissue and/or membranepotentials associated therewith may be defined as a neural stimulationintensity.

Neural stimulation intensity may be a function of pulse amplitude; pulsewidth; interpulse interval, pulse repetition and/or pulse trainrepetition frequency; pulse count; pulse polarity; and/or one or moreother parameters. In certain embodiments, power consumption and/orneural stimulation efficacy may be affected by adjusting, modifying, ormodulating a neural stimulation intensity. Such intensity-basedmodulation may occur relative to one or more time domains describedabove, for example, a subseconds-based and/or a seconds-based timedomain. Particular neural stimulation intensity modification ormodulation examples are provided hereafter.

FIG. 10A is a graph illustrating an exemplary neural stimulationintensity modulation to affect power consumption and/or neuralstimulation efficacy according to an embodiment of the invention. In oneembodiment, the neural stimulation may comprise a plurality of pulsesthat exhibit one or more types of pulse-width variation from a given orparticular pulse to another pulse. For instance, pulses within a firstpulse packet may have a first-phase pulse width that is a multiple orfraction (e.g., approximately one-half) of a first-phase pulse width ofpulses within a second pulse packet. A third pulse packet may beidentical or essentially identical to or different from the first orsecond pulse packet. Depending upon embodiment details, pulse-widthvariation may occur in a periodic, aperiodic, or pseudo-random manneracross or within a set of pulse packets. Those skilled in the art willunderstand that the pulses shown in FIG. 10A are not to scale. Thoseskilled in the art will also understand that a second pulse phase mayvary in duration in the event that a peak magnitude associated with thesecond pulse phase reaches a limit or bound.

From a patient treatment perspective, the effect(s) associated with apulse width variation may be identical, essentially identical,analogous, or similar to the effect(s) associated with an amplitude orother type of variation because both pulse width variation and amplitudevariation may alter an amount of electrical charge delivered to thepatient during a specific pulse phase or pulse subinterval.

FIG. 10B is a graph illustrating an exemplary neural stimulationintensity modulation to affect power consumption and/or neuralstimulation efficacy according to another embodiment of the invention.In one embodiment, the neural stimulation may comprise an alternatingseries of pulse packets, wherein neural stimulation intensity variesfrom one pulse packet to another. For example, a first pulse packet orgroup may comprise a first number of pulses characterized by a firstpulse repetition frequency and a first peak amplitude; and a second anda third pulse packet or group may comprise a second and a third numberof pulses, respectively characterized by at least one reduced pulserepetition frequency and at least one reduced peak amplitude.Additionally or alternatively, one or more pulses may be omitted orskipped within particular pulse packets, and/or one or more first-phasepulse widths may differ between or within pulse packets.

Modification of Spatiotemporal Stimulation Characteristics

In some embodiments, the neural stimulation may be applied in one ormore spatiotemporally varying manners to affect power consumption and/orneural stimulation efficacy. Depending upon embodiment details,particular electrode assemblies and/or electrical contacts may beselectively activated in accordance with their type, location, and/ororientation. Such selective activation may occur in a predetermined,aperiodic, or random manner. A wide variety of spatiotemporal activationpatterns may exist, possibly depending upon the nature of a patient'sneurologic dysfunction, stimulation site locations, desired efficacycharacteristics, and/or embodiment details.

Referring again to FIGS. 1A through 1C, like reference numbers indicatelike or analogous elements. In one exemplary spatiotemporal activationpattern, electrical contacts 160 carried by an electrode assembly 150may be pairwise activated in a predetermined or pseudo-random manner.FIG. 11A illustrates another exemplary spatiotemporal activation pattern300 according to an embodiment of the invention. A first set ofelectrical contacts 160 a carried by a left hemisphere electrodeassembly 154, 156 may be activated during a first seconds-based timedomain; after which a first set of electrical contacts 160 b carried bya right hemisphere electrode assembly 150, 152 may be activated during asecond seconds-based time domain; after which a second set of electricalcontacts 160 c carried by the left hemisphere electrode assembly 154,156 may be activated during a third seconds-based time domain; afterwhich a second set of electrical contacts 160 d carried by the righthemisphere electrode assembly 150, 152 may be activated during a fourthseconds-based time domain. Such varying activation patterns may continueon a predetermined, aperiodic, or quasi-random basis depending uponembodiment details.

Stimulation signal polarity variations may be considered in thecontex_(t) of spatiotemporal characteristics. FIG. 11B illustratesexemplary stimulation signal polarity variations corresponding to thespatiotemporal activation pattern shown in FIG. 11A. In particular, FIG.11B illustrates different bipolar stimulation configurations(top ofFigure), and a cathodal unipolar and anodal unipolar stimulationconfiguration (bottom of Figure), each of which may involve circuitcompletion using a remote electrode assembly that is biased at apolarity opposite or neutral with respect to the polarities shown at thebottom of FIG. 11B. Those skilled in the art will understand that a widevariety of other stimulation signal polarity variations are possible.

Combined Approaches

Two or more of the approaches described above for affecting powerconsumption and/or neural stimulation efficacy may be simultaneously orsequentially combined. Any given combination may serve to preserve orincrease neural stimulation efficacy, and/or reduce power consumption.For example, in association with a spatiotemporal activation pattern 300such as that described above with reference to FIGS. 11A and 11B, one ormore electrical contacts 160 may periodically, aperiodically, orrandomly apply or deliver a set of threshold-level and/orsuprathreshold-level pulses at one or more times, possibly during atreatment program that primarily involves subthreshold-levelstimulation. Additionally or alternatively, left and right hemispherestimulation pulse repetition frequencies may alternate between 30 Hertzand 80 Hertz; left and right hemisphere stimulation signal polarity mayalternate to apply unipolar and bipolar stimulation in a successive,aperiodic, or random manner; and/or the durations of the first, second,third, and fourth seconds-based time domains, and therefore a set ofleft hemisphere and right hemisphere duty cycles, may be equal orunequal, and/or possibly varying.

As another example, a treatment program may comprise a continuous orgenerally continuous stimulation period characterized by a varyingneural stimulation intensity; and a set of quiescent or nearly quiescentperiods, where one or more quiescent periods may correspond to aninterruption period as described above. In such an example, thecontinuous stimulation period and/or one or more quiescent periods maybe defined relative to a seconds-based, an hours-based, and/or othertype of time domain. Moreover, particular portions of the continuousstimulation period may exhibit different peak current or voltageamplitudes.

As yet another example, a treatment program may involve a set ofneuro-burst and possibly other types of stimulation periods, where oneor more interburst and/or intraburst stimulation parameters may varywith time in a predetermined, pseudo-random, and/or aperiodic manner.For instance, during a given neuro-burst stimulation period, aninterburst frequency may vary within a lower bound and an upper boundcorresponding to a type of neuro-burst stimulation under consideration.Additionally or alternatively, one or more pulse or burst polarities mayvary in accordance with cathodal unipolar, anodal unipolar, and bipolarpolarity configurations. Also, a series of intraburst pulse repetitionfrequencies may vary with time (e.g., between 100 Hz and 200 Hz in aperiodic, aperiodic, or random manner).

Essentially any of the above approaches for reducing power consumptionand/or affecting neural stimulation efficacy may be combined in avariety of manners. The resulting neural stimulation may address one ormore patient states, conditions, symptoms, and/or functional deficits inan effective, generally effective, adequate, or generally acceptablemanner.

Preprogrammed or Programmably Selectable Parameter Variation Modes

Multiple types of stimulation signal parameter variation modes may bepreprogrammed in a stimulation device such as an IPG, and/orprogrammably selected during a programming session. In certain modes,particular stimulation signal parameter variations may be based upon oroccur relative to a set of baseline or previously established parametervalues, which may be patient-specific.

Table 1 provides a list of representative types of stimulation signalparameter variation or modulation modes that may be programmablyselected in association with an IPG programming session. As indicated inTable 1, such modes may provide for multiple types of pulse widthvariation, duty cycle variation, pulse repetition frequency variation,and/or polarity variation. Other types of stimulation parametermodulation modes may also be provided in addition to or instead of thoseindicated in Table 1, possibly depending upon stimulation devicecapabilities. Certain modes may involve multiple or combined types ofstimulation signal parameter variation in a manner analogous to thatdescribed above.

Additional Neural Stimulation Efficacy and/or Power ConsumptionConsiderations

Neural stimulation efficacy may depend upon one or more stimulationparameter values. For instance, neural stimulation efficacy may be pulserepetition frequency dependent. Moreover, depending upon the nature of apatient's neurologic dysfunction, neural stimulation efficacy maydegrade or wane over time in a manner that depends upon pulse repetitionfrequency. Thus, a first pulse repetition frequency or pulse repetitionfrequency range may be associated with rapid or generally rapid onset ofsymptomatic benefit, but a short or relatively brief benefit duration orhalf-life. A second pulse repetition frequency or pulse repetitionfrequency range may be associated with a slower or delayed onset ofsymptomatic benefit, but a longer benefit duration or half-life. Theneural stimulation efficacy corresponding to the first and second pulserepetition frequencies may be essentially identical or different.

As an example, a patient exhibiting symptoms of Parkinson's Disease mayexperience rapid or reasonably rapid (e.g., approximately 10 to 30minutes after initiation of neural stimulation) and/or significantlyeffective relief from one or more symptoms for approximately 1.5 to 2.5hours in response to neural stimulation characterized by a pulserepetition frequency of approximately 30 Hertz. Neural stimulationefficacy may progressively taper off if 30 Hertz stimulation continues.Approximately 1.0 hours after initiation of the 30 Hertz neuralstimulation, application of neural stimulation characterized by a pulserepetition frequency of approximately 10 Hertz or less may result inlonger lasting or more sustained symptomatic benefit, although in somesituations such benefit may be less effective relative to the magnitudeof symptomatic relief. The 10 Hertz stimulation may also reduce powerconsumption.

FIG. 12 is a flowchart illustrating various methods for reducing powerconsumption and/or affecting neural stimulation efficacy. In oneembodiment, a method 400 comprises a first selection procedure 402 thatinvolves selecting, identifying, and/or retrieving a set of neuralstimulation parameters (NSPs); and a first determination procedure 404that involves determination, measurement, and/or estimation of a benefitonset time (BOT) and/or a benefit duration (BD) corresponding to the setof neural stimulation parameters currently under consideration. Themethod 400 may additionally comprise a second determination procedure406 that involves returning to the first selection procedure 402 in theevent that consideration of one or more additional neural stimulationparameter sets is desired.

In one embodiment, the method 400 comprises a second selection procedure408 that involves selection of a set of neural stimulation parametersthat is expected to provide or result in a rapid, reasonably rapid, oracceptable benefit onset time and an acceptable level of efficacy. Themethod 400 may further comprise a first application procedure 410 thatinvolves the application of neural stimulation signals to the patient inaccordance with the neural stimulation parameter set underconsideration, for a portion of an expected or estimated benefitduration (EBD) associated with such a parameter set. The expectedbenefit duration may correspond, for example, to an expected benefithalf-life.

The method 400 may also comprise a third selection procedure 412 thatinvolves selection of a set of neural stimulation parameters that isexpected to provide or result in a prolonged, good, or acceptablebenefit duration and an acceptable level of efficacy. The method 400 maycorrespondingly comprise a second application procedure 414 thatinvolves the application of neural stimulation signals to the patient inaccordance with the stimulation parameter set currently underconsideration.

In one embodiment, the method 400 may comprise a first evaluationprocedure 416 that involves determining whether a good, acceptable, oradequate level of efficacy is maintained or sustained relative to theneural stimulation parameter set currently under consideration. If not,the method 400 may comprise an interruption procedure 422 that involvestemporarily interrupting or pausing the application of neuralstimulation signals to the patient; and a second evaluation procedure424 that involves determining whether to resume or terminate the neuralstimulation. If resumption of neural stimulation is desired, the method400 may return to the second selection procedure 408 in one embodiment;otherwise, the method 400 may comprise a termination procedure.

In the event that a good, acceptable, or adequate level of efficacy ismaintained in view of the neural stimulation parameter set currentlyunder consideration, the method 400 may comprise a second evaluationprocedure 418 that involves determining whether the neural stimulationhas been applied beyond a time that may correspond to an expectedbenefit duration, for example, an expected or estimated benefithalf-life. If the neural stimulation has not been applied beyond such atime, the method 400 may return to the second application procedure 414.

If the neural stimulation has been applied or delivered beyond a timethat corresponds to an expected benefit duration, the method 400 maycomprise a third determination procedure 420 that involves determiningwhether consideration of another neural stimulation parameter set isdesired. If so, the method 400 may return to the second applicationprocedure 412; otherwise, the method 400 may return to the interruptionprocedure 422.

In general, neural stimulation efficacy may be maintained or enhancedwhen portions of one or more target neural populations or neuralensembles perceive applied stimulation signals as novel or generallynovel. Neural stimulation efficacy may be maintained or enhanced throughthe application of stimulation signals that vary in one or more mannersdescribed above. In certain embodiments, such variation may occur in aprogressive, cyclical, and/or ongoing manner. Progressively increasingnovelty or ongoing change may occur by successively varying greaternumbers of stimulation parameters and/or varying one or more givenstimulation parameters in a more unpredictable or complex manner withtime. In some embodiments, once the simultaneous or sequential variationof a given number of stimulation parameters has occurred, a reduction ina number of varied parameters and/or a simplification in variationcomplexity may occur. Additionally or alternatively, neural stimulationmay be temporarily interrupted or discontinued to increase a likelihooda) that the absence of neural stimulation is a novel condition for aneural population; and/or b) the application of stimulation signalsexhibiting progressively increasing novelty can resume again startingwith a small number and/or simple types of stimulation signal parametervariations. In some embodiments, stimulation parameter variation may bebased upon an extent to which symptomatic benefit has waned or degradedover time.

FIG. 13 is a flowchart illustrating various other and/or additionalmethods for affecting power consumption and/or neural stimulationefficacy. Particular methods corresponding to FIG. 13 may facilitate oreffectuate the application of stimulation signals to particular neuralpopulations in a manner that may be characterized by progressivelyincreased, augmented, and/or supplemental novelty.

In one embodiment, a method 500 comprises a first selection procedure502 that involves selection, determination, identification, and/orretrieval of a first or nex_(t) neural stimulation parameter set and/ora first or nex_(t) stimulation parameter modulation function, procedure,or scheme; and a first application procedure 504 that involves theapplication or delivery of neural stimulation signals to the patient inaccordance with the neural stimulation parameter set and/or modulationscheme currently under consideration.

The method 500 may further comprise a second selection procedure 506that involves the selection of a first, next, updated, additional, ordifferent subset of neural stimulation parameters to change, adjust,vary, or modify, and/or the selection of a first, next, updated,additional, or different stimulation parameter modulation scheme; and asecond application procedure 508 that involves application of neuralstimulation signals to the patient in accordance with the adjustedparameter subset and/or modulation scheme. Depending upon that natureand/or extent of a patient's neurologic dysfunction, patient condition,and/or embodiment details, the adjustment or modification of a selectedstimulation parameter subset may involve one or more types of neuralstimulation parameter adjustment, modification, and/or variationdescribed above.

In one embodiment, the method 500 may additionally comprise a firstevaluation procedure 510 that involves determining whether a targetstimulation signal application time (which may correspond, for example,to an expected or estimated benefit duration) and/or a minimumacceptable level of efficacy have been reached. If not, the method 500may return to the second application procedure 508. In the event that atarget stimulation signal application time and/or a minimum acceptableefficacy level have been reached, the method 500 may comprise adetermination procedure 512 that involves determining whether adjustmentor modification of the same or a different stimulation parameter subsetand/or modulation scheme is desired or warranted. If so, the method 500may return to the second selection procedure 506.

In certain embodiments, the method 500 may also comprise an interruptionprocedure 514 that involves temporarily interrupting or pausing theapplication of stimulation signals and/or one or more other portions ofa treatment program. The method 500 may further comprise a secondevaluation procedure 516 that involves determining whether to resume theapplication of stimulation signals and/or one or more portions of thetreatment program to the patient. If so, the method 500 may return tothe first selection procedure 500; otherwise, the method may comprise atermination procedure.

Stimulation Adjustment Based upon Lasting Neurofunctional Change

Neural stimulation provided, applied, or delivered in accordance withcertain embodiments of the present invention may aid and/or give rise toone or more cumulative, persistent, and/or semipersistentneurofunctional effects and/or may facilitate and/or effectuateneuroplastic changes within a patient's brain (e.g., within one or morecortical regions). Depending upon embodiment details and/or the natureof a patient's neurologic dysfunction, condition, and/or treatmenthistory, one or more of such effects and/or changes may be permanent,essentially permanent, lasting, generally lasting, persistent, and/orsomewhat persistent in the absence of neural stimulation. Additionallyor alternatively, one or more of such effects and/or changes may existto a limited extent and/or for a limited time interval after neuralstimulation is interrupted or discontinued, possibly such that theextent and/or interval of existence increases during and/or followingthe course of a treatment program. A neurofunctional effect thatpersists for a limited or increasing time period following theinterruption or cessation of neural stimulation may increase alikelihood that subsequent reduced power or less frequent neuralstimulation may provide good or adequate symptomatic benefit. Moreover,in certain situations, a persistent or generally persistentneurofunctional effect may aid in countering undesirable neuraladaptation or neural accommodation to stimulation signals, particularlysince symptomatic benefit may be achieved with less intense and/or lessfrequent stimulation as a persistent neurofunctional effect develops.

As an example, cortical stimulation may facilitate or enhance at leastpartial functional recovery of a deficit associated with stroke,traumatic brain injury, cerebral palsy, movement disorders, and/or othertypes of neurologic dysfunction on a generally lasting or long termbasis, possibly through mechanisms involving neuroplastic change. Neuralstimulation may be particularly effective at facilitating oreffectuating lasting, persistent, and/or semipersistent neurofunctionalchange when stimulation is applied in conjunction or association withone or more types of adjunctive or synergistic therapy (e.g., abehavioral therapy that is neurofunctionally relevant with respect toone or more patient states, conditions, and/or symptoms).

Neural stimulation systems and/or methods directed toward providing alasting or long term reduction in one or more neurofunctional deficitsare described in U.S. application Ser. No. 09/802,808, entitled “Methodsand Apparatus for Effectuating a Lasting Change in a Neural Function ofa Patient,” filed on Mar. 8, 2001, incorporated herein by reference.Cortical stimulation directed toward treating a set of movement disordersymptoms and/or symptoms corresponding to one or more other types ofneurologic dysfunction may facilitate a reduction in the severity ormagnitude of one or more symptoms even in the absence of suchstimulation. Cortical stimulation systems and/or methods for treatingParkinson's Disease and/or other movement disorders are described indetail in U.S. patent application Ser. No. 10/731,731, entitled “Systemand Method for Treating Parkinson's Disease and Other MovementDisorders,” filed on Dec. 9, 2003; and U.S. patent application Ser. No.10/782,526, entitled “Systems and Methods for Enhancing or OptimizingNeural Stimulation Therapy for Treating Symptoms of Parkinson's Diseaseand/or Other Neurological Dysfunction,” filed on Feb. 19, 2004.

Evidence of a lasting, persistent, or semipersistent change in a patientstate, condition, and/or functional deficit may indicate that one ormore portions of a treatment program associated with a treatment programmay be modified or varied in a manner that affects power consumptionand/or neural stimulation efficacy while retaining 1) a high or anacceptable degree of efficacy relative to one or more patient states,conditions, and/or functional deficits; and/or 2) a likelihood that themodified neural stimulation may facilitate or effectuate furtherlasting, persistent, or semipersistent change. In certain embodiments,modification of a treatment program based upon evidence of a lastingchange may comprise modification of one or more neural stimulationprocedures and/or adjunctive therapy procedures (e.g., a drug-relatedprocedure and/or a behavioral therapy procedure).

A lasting change in a patient state, condition, and/or functionaldeficit may identified, monitored, and/or measured through theacquisition and/or analysis of patient state information at one or moretimes, possibly in association with an interruption of or a parametricmodification corresponding to one or more neural stimulation and/oradjunctive therapy procedures. Such a parametric reduction may comprise,for example, a reduction in a neural stimulation dose and/or a drug doseacross one or more time domains.

Acquisition of patient state information may involve one or more patientmonitoring units 200 and/or human observation. In certain embodiments,patient state information may comprise and/or be based upon one or moretypes of electrophysiological signals such as EMG, EEG, ECoG, MEG,evoked potential, neural conduction latency, and/or other signals.Patient state information may additionally or alternatively compriseand/or be based upon one or more types of functional and/or behavioralcorrelate signals and/or behavioral assessment data. Functional orbehavioral correlate signals may comprise, for example, accelerometersignals, force and/or strain gauge signals, data and/or resultscorresponding to tests of patient performance or capability, and/orother types of signals.

In some embodiments, patient state information may comprisecerebro-muscular and/or cerebro-cerebral coherence information;cerebro-muscular and/or cerebro-cerebral partial coherence information;event-related desynchronization information; power and/or frequencyspectra information; silent period (e.g., cortical and/or peripheralsilent period) information; neural imaging (e.g., MRI, fMRI, DTI, and/orPET scan) information; and/or other measured and/or calculatedinformation or signals. Particular manners of acquiring and/orinterpreting coherence-related information are described in “Thecerebral oscillatory network of parkinsonian resting tremor,” LarsTimmermann et al., Brain (2003), Vol. 126, p. 199-212.

Depending upon embodiment details, acquisition of patient stateinformation may occur prior to and/or at the start of a treatmentprogram; at one or more time periods or intervals (e.g., at or every 3weeks; 3 months; 6 months; or 1 or more years) during or following thecourse of a treatment program; and/or in response to patient attainmentof a given level of functional performance or improvement. In variousembodiments, functional performance may be assessed and/or scored inaccordance with one or more types of standardized tests, for example,the Unified Parkinson's Disease Rating Scale (UPDRS).

Evidence of a lasting change may indicate that further lasting orpossibly lasting change and/or improved, maintained, or altered neuralstimulation efficacy may be facilitated and/or effectuated inassociation with one or more treatment program modifications. Suchtreatment program modifications may comprise procedures involving thedetermination of a new or updated initial stimulation configuration;and/or the determination of one or more new or updated adjustedstimulation configurations, which may involve one or more types ofstimulation parameter or characteristic adjustments or variationsdescribed above, and/or one or more types of procedures described above.

FIG. 14 is a flowchart illustrating various methods for adjusting,modifying, or updating a treatment program based upon evidence of acumulative, persistent, or semipersistent neurofunctional effect. In oneembodiment, a method 600 comprises an initial stimulation procedure 602that may involve applying neural stimulation to a patient in accordancewith an initial stimulation configuration associated with a treatmentprogram. The method 600 may further comprise an adjusted stimulationprocedure 604 that involves application of neural stimulation proceduresto the patient in accordance with one or more adjusted stimulationconfigurations associated with the treatment program. The method 600 mayadditionally comprise an interruption procedure 606 that involvesinterrupting one or more portions of the treatment program. Dependingupon embodiment details, the interruption procedure 606 may result in atemporary interruption of the neural stimulation, a temporaryinterruption of a drug-related procedure, and/or another type oftemporary treatment program interruption.

In one embodiment, the method 600 also comprises a monitoring procedure608 that involves determining whether evidence of a cumulative,persistent, or semipersistent neurofunctional effect exists. If not, themethod 600 may comprise a resumption decision procedure 610 thatinvolves determining whether to resume the treatment program. Iftreatment program resumption is desired, the method 600 may return tothe adjusted stimulation procedure 604 in certain embodiments;otherwise, the method 600 may comprise a termination procedure.

In the event that evidence of a cumulative, persistent, orsemipersistent neurofunctional effects exists, the method 600 maycomprise an adjustment decision procedure 612 that involves determiningwhether to adjust, modify, or vary one. or more portions of thetreatment program. If treatment program adjustment is not desired orwarranted, the method 600 may return to the resumption decisionprocedure 610.

If treatment program is adjustment is desired or warranted, the method600 may comprise an adjustment procedure 614 that involves adjusting,modifying, or varying the treatment program in one or more manners. Anadjustment procedure 614 may comprise, for example, a reduction in aneural stimulation amplitude, a pulse repetition frequency, and/or aduty cycle; specification, definition, or identification of a differentor modified set of mathematical functions or operations corresponding toone or more neural stimulation parameters; specification oridentification of a different or modified set of electrode assemblies,electrical contacts, and/or signal transfer elements that may beactivated an any given time; a reduction in a drug dose and/orspecification of a different drug; and/or a reduction or increase in anumber of behavioral therapy sessions and/or specification of anotherand/or an additional behavioral therapy. Following the adjustmentprocedure 614, in one embodiment the method 600 returns to an initialstimulation procedure.

One or more techniques or procedures for applying, varying, and/oradjusting neural stimulation to affect power consumption and/or neuralstimulation efficacy in accordance with the present invention may beinitiated or performed in view of a patient's drug or chemical substancetherapy. In some situations, there may be a delay between drugadministration and a drug onset time associated with noticeable orsignificant symptomatic benefit. Moreover, since drug levels within thebody decrease following drug administration as a drug is metabolized,patient symptoms will become more noticeable or unacceptable over time.

FIG. 15 is a flowchart illustrating various methods for affecting powerconsumption and/or neural stimulation efficacy in view of a drug and/orchemical substance therapy. In one embodiment, a method 700 comprises adrug and/or chemical substance administration procedure 702 thatinvolves the injection, ingestion, and/or other type of application ofone or more relevant substances. Such a procedure may involve, forexample, self-administration of Levodopa or dopamine agonists.

The method 700 may further comprise an initial stimulation procedure 704that involves applying neural stimulation to the patient in a mannerthat accommodates an expected drug onset time and/or an actual orexpected initial or peak level of drug benefit. The initial stimulationprocedure 704 may be time referenced or approximately synchronized to anactual or approximate drug administration time. Depending uponembodiment details, the initial stimulation procedure 704 may bedirected toward providing reduced or significantly reduced powerconsumption if the drug(s) under consideration provide significantsymptomatic benefit in the absence of neural stimulation.

The method 700 may also comprise a first evaluation procedure 706 thatinvolves determining whether a) an actual or expected drug half-lifetime has been reached or exceeded; and/or b) one or more patientsymptoms has reappeared to an extent that is undesirable problematic.One or more portions of the first evaluation procedure 706 may beperformed automatically, for example, based upon a clock or timer;and/or in response to receipt and/or analysis of a set of signalsreceived from a patient monitoring device 200 that is operativelycoupled to an IPG or stimulation signal generator. A representativepatient monitoring device 200 may comprise, for example, a motion sensoror one or more accelerometers.

In the event that a drug half-life has not been reached or exceeded,and/or a drug effect maintained at a desirable or acceptable level, themethod 700 may comprise a first adjustment procedure 708 that involvesapplying neural stimulation in accordance with one or more reduced-powerstimulation parameter sets. Thus, while patient symptoms are adequatelycontrolled or managed by the patient's drugs, an undesirable orunnecessary amount of power consumption may be avoided.

The method 700 may additionally comprise a second evaluation procedure710 that involves determining whether one or more undesirable orproblematic drug-related side effects is present. One or more portionsof the second evaluation procedure 710 may be performed manually orautomatically, in manners analogous to those indicated above. In theevent that an undesirable or problematic side effect is present, themethod 700 may comprise a second adjustment procedure 712 directedtoward varying, adjusting, or modifying the neural stimulation in amanner that at least partially counters the side effect.

In the event that a drug half-life has been reached or exceeded and/or adrug effect has degraded to an undesirable extent, the method 700 maycomprise a third adjustment procedure 714 that involves applying neuralstimulation in accordance with one or more stimulation parameter setsdirected primarily toward providing enhanced or maximal efficacy,possibly with power consumption as a secondary consideration.

In various embodiments, one or more adjustment procedures 708, 712, 714may be initiated and/or terminated in response to a signal received froma patient-controlled input device (e.g., a patient magnet or areduced-functionality external programming device). An adjustmentprocedure 708, 712, 714 may involve switching to, stepping through, orotherwise testing particular stimulation parameter sets in a manual,semi-automatic, or automatic manner. Some of such parameter sets may beprestored in or on a programmable computer medium, for example, one ormore parameter sets that were previously effective for treating patientsymptoms. In several embodiments, previously effective parameter setsmay be further modified on a manual, semi-automatic, or automatic basis,possibly in association with patient and/or patient monitoring unitinput, to enhance a likelihood of achieving or preserving symptomaticbenefit.

From the foregoing, it will be appreciated that specific embodiments ofthe invention have been described herein for purposes of illustration,but that various modifications may be made without deviating from theinvention. For example, several aspects of the invention have beendescribed in the contex_(t) of cortical electromagnetic stimulationdevices, and in other embodiments, stimulation may be provided bysubcortical devices. Aspects of the invention described in the contextof particular embodiments may be combined or eliminated in otherembodiments. For example, methods described in the context of particularneurostimulation devices may be applied to other neurostimulationdevices in other embodiments. Further, while advantages associated withcertain embodiments of the invention have been described in the contextof those embodiments, other embodiments may also exhibit suchadvantages, and not all embodiments need necessarily exhibit suchadvantages to fall within the scope of the invention. Accordingly, theinvention is not limited except as by the appended claims.

1. A method for treating a neurological condition of a patient,comprising: applying electromagnetic stimulation to a patient's nervoussystem over a first time domain with a first waveform having a first setof parameters; and applying electromagnetic stimulation to the patient'snervous system over a second time domain with a second waveform having asecond set of parameters, wherein at least one parameter of the secondset is different than a corresponding parameter of the first set.
 2. Themethod of claim 1 wherein the applying electromagnetic stimulation overat least one of the first and second time domains includes applyingelectromagnetic stimulation at sub-threshold levels.
 3. The method ofclaim 1 wherein the applying electromagnetic stimulation over at leastone of the first and second time domains includes applyingelectromagnetic stimulation at at least two of the following levels:sub-threshold, threshold, and suprathreshold.
 4. The method of claim 1,further comprising: interrupting the application of electromagneticstimulation between the first and second time domains; and selecting theat least one parameter of the second set to reduce power consumption dueto electrical stimulation during the second time domain compared withpower consumption due to electrical stimulation during the first timedomain.
 5. The method of claim 4 wherein at least one of interruptingthe application of electromagnetic stimulation and selecting the atleast one parameter includes is performed before a power source thatprovides power for the electromagnetic stimulation is significantlydepleted.
 6. The method of claim 1 wherein applying electromagneticstimulation over a second time domain includes applying electromagneticstimulation over a second time domain that is sequential to the firsttime domain.
 7. The method of claim 1 wherein applying electromagneticstimulation over the first time domain includes applying electromagneticstimulation at a first location and wherein applying electromagneticstimulation over the second time domain includes applyingelectromagnetic stimulation at a second location different than thefirst location.
 8. The method of claim 1 wherein applyingelectromagnetic stimulation over a second time domain includes applyingelectromagnetic stimulation over a second time domain that is initiatedafter initiation of the first time domain and completed beforecompletion of the first time domain.
 9. The method of claim 1 whereinapplying electromagnetic stimulation includes applying electricalstimulation over multiple second time domains that are nested within thefirst time domain.
 10. The method of claim 9 wherein the first timedomain is hours-based and the second time domain is based on a timeperiod less than hours.
 11. The method of claim 1 wherein applyingelectromagnetic stimulation during at least one of the time domainsincludes applying the electromagnetic stimulation in a manner thatvaries aperiodically.
 12. The method of claim 11 wherein applyingelectromagnetic stimulation includes applying electromagneticstimulation in a manner that varies chaotically.
 13. The method of claim11 wherein applying electromagnetic stimulation includes applyingelectromagnetic stimulation signals in a manner that corresponds atleast generally to an iterative function.
 14. The method of claim 11wherein applying electromagnetic stimulation includes applyingelectromagnetic stimulation signals in a manner that corresponds atleast generally to a partial sum of an infinite series.
 15. The methodof claim 11 wherein applying electromagnetic stimulation includesapplying electromagnetic stimulation signals in a manner thatcorresponds at least generally to a metastable attractor.
 16. The methodof claim 1 wherein selecting the at least one parameter includesselecting the at least one parameter to resume, at least approximatelymaintain, or resume and at least approximately maintain a benefitresulting from stimulation during the first time domain.
 17. Anapparatus for treating a neurological condition of a patient,comprising: a stimulation device having at least one stimulatorconfigured to be positioned in signal communication with neural tissueof a patient's nervous system; a signal generator; a signalcommunication link operatively coupled between the stimulation deviceand the signal generator; and a controller operatively coupled to thesignal generator, the controller being configured to provideinstructions to the signal generator that: direct an application ofelectromagnetic stimulation to the patient's nervous system over a firsttime domain with a first waveform having a first set of parameters; anddirect an application of electromagnetic stimulation to the patient'snervous system over a second time domain with a second waveform having asecond set of parameters, wherein at least one parameter of the secondset is different than a corresponding parameter of the first set. 18.The apparatus of claim 17 wherein the signal generator is configured todirect application of electromagnetic stimulation at sub-thresholdlevels.
 19. The apparatus of claim 17 wherein the controller includesstored instructions that direct electromagnetic stimulation over thefirst and second time domains.
 20. The apparatus of claim 17 wherein thestimulation device includes an electrode device, and wherein the atleast one stimulator includes at least one electrode.
 21. The apparatusof claim 17 wherein the signal generator includes an implantable pulsegenerator configured to be implanted in the patient.
 22. The apparatusof claim 17 wherein the signal generator includes an implantable housingconfigured to be implanted in the patient, and wherein the housingcarries a first pulse generator and a second pulse generator.
 23. Theapparatus of claim 22 wherein the first pulse generator is configured todeliver electromagnetic stimulation over the first time domain, and thesecond pulse generator is configured to deliver electromagneticstimulation over the second time domain.
 24. The apparatus of claim 22wherein the first pulse generator is configured to deliverelectromagnetic stimulation to a first location of the patient's bodyand the second pulse generator is configured to deliver electromagneticstimulation to a second location of the patient's body.
 25. Theapparatus of claim 17 wherein the controller is configured to provideinstructions that direct the application of electromagnetic stimulationover a second time domain that is sequential to the first time domain.26. The apparatus of claim 17 wherein the controller is configured toprovide instructions that direct the application of electromagneticstimulation over multiple second time domains that are nested within thefirst time domain.
 27. The apparatus of claim 17 wherein the controlleris configured to provide instructions that: interrupt the application ofelectromagnetic stimulation between the first and second time domains;and select the at least one parameter of the second set to reduce powerconsumption due to electrical stimulation during the second time domaincompared with power consumption due to electrical stimulation during thefirst time domain.
 28. The apparatus of claim 27, further comprising apower source coupled to the signal generator, and wherein at least oneof the interrupt instruction and the select instruction is providedbefore the power source is significantly depleted.
 29. An apparatus fortreating a neurological condition of a patient, comprising: animplantable stimulation device having at least one implantablestimulator configured to be positioned in signal communication withneural tissue of a patient's nervous system, the stimulation devicebeing configured to be implanted in the patient; an implantable signalgenerator; a signal communication link operatively coupled between thestimulation device and the signal generator; and a controlleroperatively coupled to the signal generator, the controller beingconfigured to provide instructions to the signal generator to direct anapplication of electromagnetic stimulation to the patient in a mannerthat varies aperiodically.
 30. The apparatus of claim 29 wherein thesignal generator is configured to direct application of electromagneticstimulation at sub-threshold levels.
 31. The apparatus of claim 29wherein the signal generator is configured to direct application ofelectromagnetic stimulation at at least two of the following levels:sub-threshold, threshold and suprathreshold.
 32. The apparatus of claim29 wherein the controller is configured to provide instructions todirect an application of electromagnetic stimulation in a manner thatvaries chaotically.
 33. The apparatus of claim 29 wherein the controlleris configured to provide instructions to direct an application ofelectromagnetic stimulation in a manner that corresponds to an iterativefunction.
 34. The apparatus of claim 29 wherein the controller isconfigured to provide instructions to direct an application ofelectromagnetic stimulation in a manner that corresponds to a partialsum of an infinite series.
 35. The apparatus of claim 29 wherein thecontroller is configured to provide instructions to direct anapplication of electromagnetic stimulation in a manner that correspondsto a metastable attractor.
 36. An apparatus for treating a neurologicalcondition of a patient, comprising: an implantable stimulation devicehaving at least one implantable stimulator configured to be positionedin signal communication with neural tissue of a patient's nervoussystem, the stimulation device being configured to be implanted in thepatient; an implantable signal generator; a signal communication linkoperatively coupled between the stimulation device and the signalgenerator; and a controller operatively coupled to the signal generator,the controller being configured to provide instructions to the signalgenerator to direct an application of electromagnetic stimulation to thepatient in a manner that varies at least generally similarly tonaturally occurring brainwave variations.
 37. The apparatus of claim 36wherein the signal generator is configured to direct application ofelectromagnetic stimulation at sub-threshold levels.
 38. The apparatusof claim 36 wherein the controller is configured to provide instructionsto direct an application of electromagnetic stimulation having a burstfrequency and an intra-burst frequency greater than the burst frequency.39. The apparatus of claim 36 wherein the controller is configured toprovide instructions to direct an application of electromagneticstimulation having a burst frequency and an intra-burst frequencygreater than the burst frequency, and wherein characteristics of theintra-burst stimulation vary from one burst to another.
 40. Theapparatus of claim 36 wherein the controller is configured to provideinstructions to direct an application of electromagnetic stimulationwith an inter-burst frequency that is generally similar to naturallyoccurring alpha brainwave frequencies, wherein the inter-burst frequencyhas a value of from about 8 Hz to about 13 Hz.
 41. The apparatus ofclaim 36 wherein the controller is configured to provide instructions todirect an application of electromagnetic stimulation with an inter-burstfrequency that is generally similar to naturally occurring betabrainwave frequencies, wherein the inter-burst frequency has a value offrom about 13 Hz to about 30 Hz.
 42. The apparatus of claim 36 whereinthe controller is configured to provide instructions to direct anapplication of electromagnetic stimulation with an inter-burst frequencythat is generally similar to naturally occurring gamma brainwavefrequencies, wherein the inter-burst frequency has a value of greaterthan about 30 Hz.
 43. The apparatus of claim 36 wherein the controlleris configured to provide instructions to direct an application ofelectromagnetic stimulation with an inter-burst frequency that isgenerally similar to naturally occurring delta brainwave frequencies,wherein the inter-burst frequency has a value of less than about 4 Hz.44. The apparatus of claim 36 wherein the controller is configured toprovide instructions to direct an application of electromagneticstimulation with an inter-burst frequency that is generally similar tonaturally occurring theta brainwave frequencies, wherein the inter-burstfrequency has a value of from about 4 Hz to about 8 Hz.